space travel health risks

NASA scientists consider the health risks of space travel

NASA astronauts Tom Marshburn (at left) and Kayla Barron are seen outside of the Quest airlock at the International Space Station during a spacewalk on Thursday, Dec. 2, 2021. Experts are continuing to study how space affects the human body.

Humans aren't built to live in space, and being there can pose serious health risks . For space administrations like NASA, a major goal is to identify these risks to hopefully help lessen them.

That was a major theme during NASA’s Spaceflight for Everybody Virtual Symposium in November, a virtual symposium dedicated to discussing current knowledge and research efforts around the impact of spaceflight on human health. During a panel discussion titled “Human Health Risks in the Development of Future Programs” on Nov. 9, NASA scientists discussed these risks and how they are using existing knowledge to plan future missions.

Each panelist emphasized that the health risks presented by space travel are complex and multifaceted and that all types of risks should be considered closely when planning future missions.

Related: Space travel can seriously change your brain

Five types of risk

When discussing the risks presented by living in space and space travel, there are five main types, the scientists outlined in the presentation.

Two types of risk, radiation and altered gravity, come simply from being in space, they said. Research has shown that both can have major negative effects on the body, and even the brain . Others, like isolation and confinement as well as being in a hostile closed environment, encompass risks posed by the living situations that are necessary in space, including risks to both mental and physical health.

Then, there are the risks presented simply by being a long way from Earth. The farther humans get from the Earth, the riskier living in space becomes in almost every way.

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Everything from fresh food to unexpired medication will be extremely difficult to make accessible with longer journeys farther away. On the International Space Station, astronauts aren’t too far from us, and we can routinely send supplies to the crews in orbit. But a mission to the moon or Mars would pose more problems.

Communication delays would increase, and there would likely be communication blackouts, said Sharmi Watkins, assistant director for exploration in NASA’s Human Health and Performance Directorate who served as a panelist for this discussion. She said it would also take longer to get back to Earth if there was a medical emergency.

"We're not going to measure it in hours, but rather in days, in the case of the moon, and potentially weeks or months, when we start to think about Mars," said Watkins.

Steve Platts, the chief scientist in NASA’s human research program, broke down different levels of risk in space and discussed how NASA uses a "phased approach" when it comes to research on human health. In this approach, initial "phases" include research on the health effects of being in space has also been done in simulated conditions on Earth, from isolation experiments in Antarctica to radiation exposure at Brookhaven National Laboratory in Long Island, New York. Likewise, experiments on the space station will help us to prepare for risk on the moon and Mars — these later phases build on knowledge gained from simulations.

"We do work on Earth, we do work on low earth orbit and then we'll be doing lunar missions, all to help us get to Mars," Platts said.

— Deep-space radiation could cause have big impacts on the brain, mouse experiment shows

— Without gravity, the fluid around an astronaut's brain moves in weird ways

— Long space missions can change astronaut brain structure and function

Still, no matter how much we may prepare on Earth, every space mission comes with risk, so NASA has set health standards to minimize this risk for astronauts.

NASA has over 800 health standards that they’ve developed based on current research. These standards describe everything from how much space astronauts should have in a spacecraft to how much muscle and bone loss an astronaut can experience without being seriously harmed. These standards also include levels of physical fitness and health the astronauts need to meet before going into space. All of NASA’s health standards for astronauts are available online .

A mission can impact astronauts’ health, but it also works the other way — health troubles with astronauts could impact a mission if they aren’t able to perform mission tasks adequately, said Mary Van Baalen, acting director of human system risk management at NASA and the panel’s moderator. She emphasized the complex interplay between these two types of impacts, both of which NASA scientists must keep in mind when planning missions.

"Space travel is an inherently risky endeavor," she said. "And the nature of human risk is complex."

You can watch the full recording of the panel discussion and other talks from the symposium here .

Join our Space Forums to keep talking space on the latest missions, night sky and more! And if you have a news tip, correction or comment, let us know at: [email protected].

Rebecca Sohn is a freelance science writer. She writes about a variety of science, health and environmental topics, and is particularly interested in how science impacts people's lives. She has been an intern at CalMatters and STAT, as well as a science fellow at Mashable. Rebecca, a native of the Boston area, studied English literature and minored in music at Skidmore College in Upstate New York and later studied science journalism at New York University.

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Scientists Release Largest Trove of Data on How Space Travel Affects the Human Body

A collection of 44 new studies, largely based on a short-duration tourist trip in 2021, provides insight into the health effects of traveling to space

Will Sullivan

Daily Correspondent

Two astronauts in space with their hair standing up and the Earth behind them

More and more humans are traveling to space. Several missions in 2021 took private citizens on tourist flights. Last month, six people flew to the edge of Earth’s atmosphere and back. NASA plans to put astronauts back on the moon later this decade, and SpaceX recently tested a rocket it hopes will one day carry humans to Mars.

With even more ambitious crewed flights on the horizon, scientists want to better understand the effects that space’s stressors—such as exposure to radiation and a lack of gravity—have on the human body. Now, a newly released set of 44 papers and troves of data, called the Space Omics and Medical Atlas (SOMA), aims to do just that.

SOMA is the largest collection of data on aerospace medicine and space biology ever compiled. It dramatically expands the amount of information available on how the human body changes during spaceflight. And the first studies to come out of this project improve scientists’ understanding of how space travel affects human health.

“This will allow us to be better prepared when we’re sending humans into space for whatever reason,” Allen Liu , mechanical engineer at the University of Michigan who is not involved in the project, tells Adithi Ramakrishnan of the Associated Press (AP).

Much of the new atlas is based on data collected from the four members of the Inspiration4 mission , a space tourism flight that sent four civilians on a three-day trip to low-Earth orbit in September 2021. The findings suggest people on short-term flights experience some of the same health impacts that astronauts face on long-term trips to space.

“We don’t yet fully understand all of the risks” of long-duration space travel, Amy McGuire , a biomedical ethicist at Baylor College of Medicine who did not contribute to the work, says to Science ’s Ramin Skibba. “This is also why it is so important that early space tourists participate in research.”

Space travel poses a number of risks to health. Without Earth’s atmosphere and magnetic field to protect them, astronauts are exposed to space radiation , which can increase their risk for cancer and degenerative diseases. Fluid shifts into astronauts’ heads when they are experiencing weightlessness, which can contribute to vision problems , headaches and changes in the structure of the brain . The microgravity environment can also lead to a loss of bone density and atrophied muscles , prompting long-haul astronauts to adopt specific exercise regimens .

But on top of those known risks, the new research highlights other potential issues. One study published Tuesday in the journal Nature Communications found that mice exposed to a dose of radiation meant to simulate a round trip to Mars experienced kidney damage and dysfunction. Human travelers might need to be on dialysis on the way back from the Red Planet if they were not protected from this radiation, writes the Guardian ’s Ian Sample.

“It’s likely to be a serious issue,” Stephen Walsh , a co-author of the study and clinician scientist at University College London, tells the publication. “It’s very hard to see how that’s going to be okay.”

The health information from the Inspiration4 astronauts sheds light on how space travel can affect private citizens who have not extensively trained for it. The findings also highlight changes to cells and DNA that can occur during short trips to space.

Biomarkers that changed during the Inspiration4 mission returned to normal a few months after the trip, suggesting that space travel doesn’t pose a greater risk to civilians than it does for trained astronauts, Christopher Mason , a geneticist at Cornell University who helped put together the atlas, says to New Scientist ’s Clare Wilson.

The Inspiration4 research also suggests women may recover faster from space travel than men. Data from the mission’s two male and two female participants, along with data from 64 NASA astronauts, indicated that gene activity related to the immune system was more disrupted in male astronauts, per the Guardian . And men’s immune systems took longer to return to normal once back on Earth.

Taken together, the new papers could help researchers learn how to ameliorate the harms space travel can cause, Afshin Beheshti , a co-author of the work and a researcher with the Blue Marble Space Institute of Science, says to the AP.

And the scientists say nothing in the data suggests humans should not go to space.

“There’s no showstopper,” Mason tells the Washington Post ’s Joel Achenbach. “There’s no reason we shouldn’t be able to safely get to Mars and back.”

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Will Sullivan is a science writer based in Washington, D.C. His work has appeared in Inside Science and NOVA Next .

Astronaut medical records reveal the health toll of space travel

The largest collection yet of detailed medical data and tissue samples from astronauts should help researchers better understand the impacts of space flight on health

By Clare Wilson

11 June 2024

Astronauts Robert L. Curbeam Jr. (left) and Christer Fuglesang on the International Space Station

More light could be shed on how space flight affects astronauts’ health after the creation of the first “space-omics” biobank – a collection of thousands of blood and tissue samples, plus medical information, taken over multiple space missions.

These include missions to the International Space Station, as well as the first all-civilian space flight, SpaceX’s Inspiration4 , which took four non-government-trained astronauts into space for three days in 2021.

Called the Space Omics and Medical Atlas (SOMA), the resource contains detailed medical data, such as on DNA damage and changes in people’s gene activity and immune system functioning, collectively known as biomarkers.

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Space flight is known to pose certain health risks. For instance, astronauts lose bone density and muscle mass due to the lack of gravity, and higher levels of radiation in space seem to cause cell and DNA damage, which have a range of impacts on the body. These effects may be why astronauts are more prone to developing heart disease in later life and some have experienced worsening vision after being in space.

Collecting astronauts’ medical data in a consistent way via the SOMA biobank will help researchers understand more about these changes and potentially develop ways to mitigate them, says Christopher Mason at Weill Cornell Medicine in New York, who helped put the biobank together.

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“Biomarkers don’t always translate into anything that’s clinically meaningful, but it’s a nice way to start to understand how this unique environment is impacting us,” says Damian Bailey at the University of South Wales in the UK, who wasn’t involved in the work.

One insight from the Inspiration4 mission is that, despite the astronauts experiencing a host of biomarker changes, most measurements returned to normal within a few months of them coming back to Earth .

This suggests that sending civilians into space doesn’t pose more health risks than sending professional astronauts, says Mason. “Instead of people training for decades to go, we could start to really open up space towards more and more people.”

The results from Inspiration4, which was crewed by two men and two women, also suggest that the changes in gene activity returned to normal faster in the women. That may be because women’s bodies have to be able to cope with a potential pregnancy , says Mason. “Being able to tolerate large changes in physiology and fluid dynamics may be great for being able to manage pregnancy, but also manage the stress of spaceflight.”

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Timothy Etheridge at the University of Exeter in the UK says it will be helpful for researchers around the world to have a common resource they can use. “You need to have a consistent approach to collecting samples,” he says.

Thomas Smith at King’s College London says understanding the health impacts of space flight will become more important if longer missions happen, such as journeys to Mars. “Anything that leads to extended duration missions, it’s more important to know what’s going on and, ideally, address it,” he says.

Journal reference:

Nature DOI: 10.1038/s41586-024-07639-y

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Human spaceflight’s new era is fraught with medical and ethical questions.

Even short trips to space have lasting effects on the average human, private missions hint

Four private individuals blasted off to the International Space Station in 2022 as part of the commercial Axiom-1 mission. As such flights become more prevalent, they bring a host of biomedical and ethics issues to the forefront.

Space lengthens human telomeres

Perhaps the most well-known long-term biomedical NASA study involved identical twins Scott and Mark Kelly ( SN: 4/11/19 ). Researchers looked at how Scott’s 340-day stay on the International Space Station affected his physiology, gene expression, immune system and mental reasoning compared with Mark, who stayed on the ground.

One fascinating finding from the study was that Scott Kelly’s telomeres got longer. Telomeres are short bits of repeating nucleic acids found at the end of DNA that act sort of like a shoelace cap, protecting the DNA strand. As cells divide, telomeres get shorter, a process thought to be associated with aging. But this didn’t mean that Kelly was getting younger while in space. In fact, he was potentially being put at risk of cancer.

Certain types of cancer “protect telomere lengths or cause telomere elongation,” says Eliah Overbey, a professor of bioastronautics at the University of Austin in Texas. “That’s part of why these cancers are tricky, because they’ll divide, divide, divide, but their telomeres aren’t getting any shorter.” Fortunately for Scott Kelly, once he returned to Earth, his telomeres shrank back to their preflight size.

But the experiment was limited by its tiny sample size.

“NASA didn’t repeat these sorts of studies on their future crews,” Overbey says. “They could be performing this routinely if they wanted, but they’re not pursuing this line of research very aggressively.”

Teleomere length, along with other molecular changes, including those related to immune response, DNA repair and stress, are data that Overbey and colleagues have collected with SOMA. And the data show that the short-term space jaunts, only three days, undergone by commercial crews such as Inspiration4 can have genetic effects not all that different from those of longer-term missions.

For the Inspiration4 crew, their telomeres lengthened during their short adventure and then returned to normal on the ground. “Even though they were only up there for three days, we were actually still able to see what was a pretty dramatic effect,” Overbey says.

Many other molecular changes followed similar patterns as the Twin Study, shifting during spaceflight for both short- and long-term flights and then largely returning to baseline once back on Earth, the SOMA data suggest.

What this means for astronaut health isn’t yet entirely clear, especially when projecting to the much longer timescales that a Mars mission or stays at a moon base might involve. Despite an increase in the number of people going to space, the sample sizes remain small, given that each of the new private missions has carried a crew of four. Even still, Overbey and her colleagues intend SOMA to become a hub for data on commercial and government crewed missions that can help answer pressing health questions.

“I view a lot of these datasets as hypothesis-generating machines,” she says.

Limited regulations raise ethical quandaries

But increasing the number of private individuals headed to space involves a host of ethical problems. Professional astronauts are continually checked by specially-trained physicians in order to continue going to orbit while, in general, the most important thing a commercial spaceflight participant needs is lots of money. And the U.S. government doesn’t currently have any health requirements for such individuals.

In order to give the nascent private space industry time to develop and gain experience without too much interference, Congress passed a moratorium on new safety regulations for commercial human spaceflight in 2004. The moratorium was originally set to expire in 2012 but has been extended multiple times, most recently to January 2025 with several proposed bills potentially pushing this date back for up to six more years.

This means that the Federal Aviation Administration, or FAA, which oversees launch licenses, doesn’t have the ability to mandate that private individuals undergo a health screening before strapping into a rocket seat.

“If you want to climb Mount Everest, you need to submit a health certificate,” says Dana Tulodziecki, a philosopher at Purdue University in West Lafayette, Ind. “That’s more than you currently officially need to do to go to space.”

Two people in zero-gravity monitor scientific equipment

The FAA suggests that private astronauts consult with a physician, who they recommend be trained in spaceflight issues, prior to flying. But there’s nobody checking to make sure that happens. And even if a doctor nixed a person from signing up for a commercial flight, what’s to stop that person from simply finding another doctor to okay them?

“These are obviously really complicated issues,” Tulodziecki says, noting that lawmakers should start figuring out what they need to consider about who should be allowed to fly on private missions long before the moratorium on regulations expires.

“There are lots of space ethics efforts that think about really large issues; political systems on other planets and whatnot,” she says. “But that’s really far in the future, right? This one is already here, it’s already happening. So, it’s really something urgent.”

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The many, many reasons space travel is bad for the human body

Leaving earth upends almost every system inside of us.

After the astronaut Scott Kelly spent a year on the International Space Station, he returned to Earth shorter, more nearsighted, lighter and with new symptoms of heart disease that his identical twin brother did not share. (Mark Kelly, now a U.S. senator, also spent a brief time in space.)

Even their DNA diverged, as nearly 1,000 of Scott Kelly’s genes and chromosomes worked differently. (On the upside, he aged about 9 milliseconds less that year, thanks to how fast the space station circled the Earth.)

Most of these effects cleared up within a few months, but not all — underscoring the potential health hazards of space travel, many of which are unknown. These will ratchet up during ambitious future trips, such as NASA’s planned Artemis mission to the moon and later travel to Mars.

Even a partial list of the likely physical and emotional consequences of deep space travel is daunting.

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Space motion sickness sets in almost immediately. The nausea, dizziness, headaches and confusion can linger for days.

“Puffy Face Bird Leg Phenomenon” develops, as blood and other bodily fluids rush to the upper body in low gravity and stay there, swelling heads and shrinking legs.

Astronauts’ appearances can change as their faces swell. The astronauts may feel congested, as though they have a constant head cold.

Muscles atrophy by as much as 1 percent every week in weightlessness, especially in the legs.

Blood volume drops — and with less blood to pump, the heart weakens and loses its signature heart shape, growing more rounded.

Like any other muscle, the heart doesn’t need to work as hard in microgravity and will begin to atrophy without rigorous exercise.

Doused with radiation, many immune cells die and immunity is lowered. There’s also DNA damage, potentially upping cancer risk.

Inflammation spikes throughout the body, possibly contributing to heart disease and other conditions.

Bones thin by about 1.5 percent a month. Spinal discs harden.

In the head, parts of the eyeball can flatten, causing sharper distance vision and dimmer near vision.

Fluids flood the skull, diminishing smell and hearing.

Gene activity changes, including in the brain. In mice, 54 different genes in the brain worked differently after weeks in space.

Brain cells can be affected by radiation, diminishing memory and thinking (in mice).

Circadian rhythms falter, making insomnia common.

Finally, months or years of solitude — or close confinement with fellow astronauts — can lead to lasting psychological stress.

“Space is just not very hospitable to the human body,” said Emmanuel Urquieta, chief medical officer at the Translational Research Institute for Space Health in Houston, which partners with NASA to study the effects of deep space exploration.

Humans evolved in conditions of plentiful gravity and relatively slight background radiation, he said. Space is the reverse and it upends the operations of almost every biological system inside of us. —

Most of the potential health risks of space travel can be mitigated to some extent, scientists point out. Exercise, for instance, “is quite effective” at helping astronauts maintain muscle mass and bone density, said Lori Ploutz-Snyder, the dean of the University of Michigan School of Kinesiology. She was previously a researcher at NASA, where she led studies of exercise and space travel.

The New Space Age

On the space station, astronauts routinely work out for about an hour most days, she said, using specialized devices to run, cycle and lift weights, despite being weightless. But on lunar and Mars missions, which will involve smaller ships and possibly years-long durations, exercise equipment will need to be shrunk and astronauts’ willingness to keep up with the workouts enlarged.

[ To counter the effect of sitting too much, try the astronaut workout ]

The Earth’s magnetic field shields the relatively close-in space station as well from some of the worst deep-space radiation, but the lunar and Mars missions — higher and farther from Earth — will not enjoy that protection.

The moon and Mars journeys will demand advanced shielding, Urquieta said, together with drugs and supplements that might lessen some of the internal effects of the remaining — and inevitable — radiation. Antioxidants, such as vitamins C and E, could sop up a portion of the damaging molecules released after radiation exposure, while other protective drugs and nutrients are under investigation, he said.

Despite every available precaution and protection, deep space will remain a harsh, unwelcoming place for the human body. But it will also, and always, represent something else for the human imagination, Urquieta said — its endless sweep of sequined darkness sparking our ambitions, dreams and stories.

Which is why, even knowing better than most people the toll such a trip might take on him, he would go into space “in a heartbeat,” he said. “Absolutely. No question. It’s so inspiring. It’s space."

About this story

Additional design and development by Betty Chavarria. Editing by Kate Rabinowitz, Manuel Canales and Jeff Dooley. Copy editing by Wayne Lockwood.

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Human Health during Space Travel: State-of-the-Art Review

Chayakrit krittanawong.

1 Department of Medicine and Center for Space Medicine, Section of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA

2 Translational Research Institute for Space Health, Houston, TX 77030, USA

3 Department of Cardiovascular Diseases, New York University School of Medicine, New York, NY 10016, USA

Nitin Kumar Singh

4 Biotechnology and Planetary Protection Group, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA

Richard A. Scheuring

5 Flight Medicine, NASA Johnson Space Center, Houston, TX 77058, USA

Emmanuel Urquieta

6 Department of Emergency Medicine and Center for Space Medicine, Baylor College of Medicine, Houston, TX 77030, USA

Eric M. Bershad

7 Department of Neurology, Center for Space Medicine, Baylor College of Medicine, Houston, TX 77030, USA

Timothy R. Macaulay

8 KBR, Houston, TX 77002, USA

Scott Kaplin

9 Department of Dermatology, Baylor College of Medicine, Houston, TX 77030, USA

Stephen F. Kry

10 Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Thais Russomano

11 InnovaSpace, London SE28 0LZ, UK

Marc Shepanek

12 Office of the Chief Health and Medical Officer, NASA, Washington, DC 20546, USA

Raymond P. Stowe

13 Microgen Laboratories, La Marque, TX 77568, USA

Andrew W. Kirkpatrick

14 Department of Surgery and Critical Care Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada

Timothy J. Broderick

15 Florida Institute for Human and Machine Cognition, Pensacola, FL 32502, USA

Jean D. Sibonga

16 Division of Biomedical Research and Environmental Sciences, NASA Lyndon B. Johnson Space Center, Houston, TX 77058, USA

Andrew G. Lee

17 Department of Ophthalmology, University of Texas Medical Branch School of Medicine, Galveston, TX 77555, USA

18 Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX 77030, USA

19 Department of Ophthalmology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

20 Department of Ophthalmology, Texas A and M College of Medicine, College Station, TX 77807, USA

21 Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA

22 Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine, New York, NY 10021, USA

Brian E. Crucian

23 National Aeronautics and Space Administration (NASA) Johnson Space Center, Human Health and Performance Directorate, Houston, TX 77058, USA

Associated Data

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans’ natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

1. Introduction

Until now space missions have generally been either of short distance (Low Earth Orbit—LEO) or short duration (Apollo Lunar Missions). However, upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX) have already started the process of preparing for long distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s [ 1 ].

Within the extraterrestrial environment, a multitude of exogenous and endogenous processes could potentially impact human health in several ways. Examples of exogenous processes include exposure to space radiation and microgravity while in orbit. Space radiation poses a risk to human health via a number of potential mechanisms (e.g., alterations of gut microbiome biosynthesis, accelerated atherosclerosis, bone remodeling, and hematopoietic effects) and prolonged microgravity exposure presents additional potential health risks (e.g., viral reactivation, space motion sickness, muscle/bone atrophy, and orthostatic intolerance) [ 2 , 3 , 4 , 5 , 6 , 7 ]. Examples of endogenous processes potentially impacted by space travel include alteration of humans’ natural circadian rhythm (e.g., sleep disturbances) and mental health disturbances (e.g., depression, anxiety) due to confinement, isolation, immobilization, and lack of social interaction [ 8 , 9 , 10 ]. Finally, the risk of unknown exposures, such as yet undiscovered pathogens, remain persistent threats to consider. Thus, prior to the emergence of long distance, long duration space travel it is critical to anticipate the impact of these varied environmental factors and identify potential mitigating strategies. Here, we review the available medical literature on human experiments conducted during space travel and summarize our current knowledge on the effects of living in space for both short and long durations of time. We also discuss the potential countermeasures currently employed during interstellar travel, as well as future directions for medical research in space.

1.1. Medical Screening and Certification Prior to Space Travel

When considering preflight medical screening and certification, the requirements and recommendations vary based on the duration of space travel. Suborbital spaceflight, part of the new era of space travel, has participants launching to the edge of space (defined as the Karman line, 100 Km above mean sea level) for brief 3–5 min microgravity exposures. Orbital spaceflight, defined as microgravity exposure for up to 30 days, involves healthy individuals with preflight medical screening. In addition to a physical examination and metabolic screening, preflight medical screening assessing aerobic capacity (VO 2max ), and muscle strength and function may be sufficient to ensure proper conditioning prior to mission launch [ 11 , 12 , 13 , 14 ]. Age-appropriate health screening tests (e.g., colonoscopy, serum prostate specific antigen in men, and mammography in women) are generally recommended for astronauts in the same fashion as their counterparts on Earth. In individuals with cardiovascular risk factors or with specific medical conditions, additional screening may be required [ 15 ]. The goal of these preflight screening measures is to ensure that medical conditions that may result in sudden incapacitation are identified and either disqualified or treated before the mission begins. In addition to the medical screening described above, short-duration space travelers are also required to undergo acceleration training, hypobaric and hypoxia exposure training, and hypercapnia awareness procedures as part of the preflight training phase.

In preparation for long-duration space travel, astronauts generally undergo a general physical examination, as well as imaging and laboratory studies at the time of initial selection. These screening tests would then be repeated annually, as well as upon assignment to an International Space Station (ISS) mission. ISS crew members are medically certified for long-duration spaceflight missions through individual agency medical boards (e.g., NASA Aerospace Medical Board) and international medical review boards (e.g., Multilateral Space Medicine Board) [ 16 , 17 ]. In order for an individual to become certified for long-duration space travel, an individual must be at the lowest possible risk for the occurrence of medical events during the preflight, infight, and postflight periods. Following spaceflight, it is recommended that returning astronauts undergo occupational surveillance for the remainder of their lifetime for the detection of health issues related to space travel (e.g., NASA’s Lifetime Surveillance of Astronaut Health program) [ 18 ]. Table 1 summarizes the preflight, inflight, and postflight screening recommendations for each organ system. Further research utilizing data from either long-term space missions or simulated environments is required in order to develop an adequate preflight scoring system capable of predicting inflight and postflight health outcomes in space travelers based on various risk factors.

Summarizes the pre-flight, in-flight and post-flight screening in each system.

Below we discuss potential Space Hazards for each organ system along with possible countermeasures ( Table 2 ). Table 3 lists prospective opportunities for artificial intelligence (AI) implementation.

Summary of Space Hazards to each organ system and potential countermeasures.

Potential AI applications in space health.

1.2. Effects on the Cardiovascular System

During short-duration spaceflight, microgravity alters cardiovascular physiology by reducing circulatory blood volume, diastolic blood pressure, left ventricular mass, and cardiac contractility [ 42 , 123 ]. Several studies have demonstrated that peak exercise performance is reduced both inflight and immediately after short-duration spaceflight due primarily to a reduction in maximal cardiac output and O 2 delivery [ 124 , 125 ]. Prolonged exposure to microgravity does cause unloading of the cardiovascular system (e.g., removal of expected loading effects from Earth’s gravity when upright during the day), resulting in cardiac atrophy. These changes may be an example of adaptive physiologic changes (“physiologic atrophy”) that returns to baseline after returning from spaceflight. This process may be similar to the adaptive physiologic changes to the cardiovascular system seen during athletic training (“physiologic hypertrophy”). Thus far, there is no evidence that the observed short-term cardiac atrophy could permanently impair systolic function. However, this physiologic adaptation to microgravity in space could lead to orthostatic hypotension/intolerance upon returning to Earth’s gravity due to changes in the comparative position of peripheral resistance and sympathetic nerve activity [ 41 , 126 , 127 ]. Figure 1 demonstrates potential effects of the space environment on each organ system.

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Potential effects of the space environment on each organ system.

Another potential effect of microgravity exposure is that an alteration of hydrostatic forces in the vertical gravitational (Gz) axis could lead to the formation of internal jugular vein thromboses [ 28 , 29 ]. Anticoagulation would not be an ideal choice for prevention as astronauts have an increased risk of suffering traumatic injury during spaceflight, thus potentially inflating the risk of developing an intracerebral hemorrhage or subdural hematoma. In addition, if a traumatic accident were to occur during spaceflight, the previously discussed cardiovascular adaptations could impair the body’s ability to tolerate blood loss and shock [ 45 , 46 , 47 ].

During long-duration spaceflight, one recent study demonstrated that astronauts did not experience orthostatic hypotension/intolerance during routine activities or after landing following 6 months in space [ 128 ]. It is worth noting that all of these astronauts performed aggressive exercise countermeasures while in flight [ 128 ]. Another study of healthy astronauts after 6 months of space travel showed that the space environment caused transient changes in left atrial structure/electrophysiology, increasing the risk of developing atrial fibrillation (AF) [ 129 ]. However, there was no definitive evidence of increased incidence of supraventricular arrhythmias and no identified episodes of AF [ 129 ]. Evaluation with echocardiography or cardiac MRI may be considered following long-duration spaceflight in certain cases.

Prior human studies with supplemental data obtained from animal studies, have shown that healthy individuals with prolonged exposure to ionizing radiation may be at increased risk for the development of accelerated atherosclerosis secondary to radiation-induced endothelial damage and a subsequent pro-inflammatory response [ 3 , 4 , 57 , 58 , 59 , 60 , 123 ]. One study utilizing human 3D micro-vessel models showed that ionizing radiation inhibits angiogenesis via mechanisms dependent on the linear energy transfer (LET) of charged particles [ 130 ], which could eventually lead to cardiac dysfunction [ 131 , 132 ]. In fact, specific characteristics of the radiation encountered in space may be an important factor to understanding its effects. For example, studies of pediatric patients undergoing radiotherapy have shown an increase in cardiac-related morbidity/mortality due to radiation exposure, but not until radiation doses exceeded 10 Gy [ 133 ]. At lower dose levels the risk is less clear: while a study of atomic bomb survivors with more than 50 years of followup demonstrated elevated cardiovascular risks at doses < 2 Gy [ 134 ]. A recent randomized clinical trial with a 20-year follow-up showed no increase in cardiac mortality in irradiated breast cancer patients with a median dose of 3.0 Gy (1.1–8.1 Gy) [ 135 ]. The uncertainty in cardiovascular effects of ionizing radiation, are accentuated in a space environment as the type and quality of radiation likely play an important role as well.

Further research is required to understand the radiation dosage, duration, and quality necessary for cardiovascular effects to manifest, as well as develop preventive strategies for AF and internal jugular vein thrombosis during space travel.

1.3. Effects on the Gastrointestinal System

During short-duration spaceflight, the presence of gastrointestinal symptoms (e.g., diarrhea, vomiting, and inflammation of the gastrointestinal tract) are common due to microgravity exposure [ 35 , 136 , 137 ]. Still unknown however is whether acute, surgical conditions such as cholecystitis and appendicitis occur more frequently due to microgravity-induced stone formation or alterations in human physiology/anatomy, and immunosuppression [ 40 ]. Controlling for traditional risk factors associated with the development of these conditions (e.g., adequate hydration, maintenance of a normal BMI, dietary fat avoidance, etc.) may help mitigate the risk.

During long-duration spaceflight, it is possible that prolonged radiation exposure could lead to radiation-induced gastrointestinal cancer. Gamma radiation exposure is a known risk factor for colorectal cancer via an absence of DNA methylation [ 138 ]. NASA has recently developed a space radiation simulator, named the “GCR Simulator”, which allows for the more accurate radiobiologic research into the development and mitigation of radiation-induced malignancies [ 139 ]. Preflight colorectal cancer screening via colonoscopy or inflight screening via gut microbiome monitoring may be beneficial, but further research is required to demonstrate their clinical utility. Several studies, including the NASA Twins study have shown that microgravity could lead to alterations in an individual’s gut microbial community (i.e., gut dysbiosis) [ 2 , 140 , 141 , 142 ]. While changes to an individual’s gut microbiome can cause inflammation of the gastrointestinal tract [ 143 , 144 ], it remains unclear whether the specific alterations observed during spaceflight pose a risk to astronaut health. In fact, increased gut colonization by certain bacterial species is even associated with a beneficial effect on the gastrointestinal tract [ 2 , 140 ]. ( Table S1 ) Certain limitations of these studies, such as variations in genomic profile, diet, and a lack of adjusted confounders (e.g., the microbial content of samples) should be considered. Another potential consequence of prolonged microgravity exposure is the possibility of increased fatty-acid processing [ 145 ], leading to the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis [ 146 , 147 ].

Further research is required to better understand gut microbial dynamics during space travel, as well as spaceflight-associated risk factors for the development of NAFLD, cholecystitis, and appendicitis.

1.4. Effects on the Immune System

During spaceflight, exposure to microgravity could potentially induce modifications in the cellular function of the human immune system. For example, it has been hypothesized that microgravity exposure could lead to an increase in the production of inflammatory cytokines [ 148 ] and stress hormones [ 149 , 150 ], alterations in the function of certain cell lines (NK cells [ 151 , 152 ], B cells [ 153 ], monocytes [ 154 ], neutrophils [ 154 ], T cells [ 5 , 155 ]), and impairments of leukocyte distribution [ 156 ] and proliferation [ 155 , 157 , 158 ]. The resultant immune system dysfunction could lead to the reactivation of latent viruses such as Epstein-Bar Virus (EBV), Varicella-Zoster Virus (VZV), and Cytomegalovirus (CMV) [ 31 , 32 ]. Persistent low-grade pro-inflammatory responses microgravity could lead to space fever. [ 159 ] Studies are currently underway to evaluate countermeasures to improve immune function and reduce reactivation of latent herpesviruses [ 33 , 160 , 161 , 162 ]. Microgravity exposure could also lead to the development of autoantibodies, predisposing astronauts to various autoimmune conditions [ 136 , 163 ]. ( Table S2 ) Most importantly, studies have shown that bacteria encountered within the space environment appear to be more resistant to antibiotics and more harmful in general compared to bacteria encountered on Earth [ 164 , 165 ]. This is in addition to the threat of novel bacteria species (e.g., Methylobacterium ajmalii sp. Nov. [ 76 ]) that we have not yet discovered.

Upon returning from the space environment astronauts remain in an immunocompromised state, which has been particularly problematic in the era of the COVID-19 pandemic. Recently, NASA has recommended postflight quarantine and immune status monitoring (i.e., immune-boosting protocol) to mitigate the risk of infection [ 77 ]. This is similar to the Apollo and NASA Health Stabilization Programs that helped establish the preflight protocol (pre-mission quarantine) currently used for this purpose.

Further research is required to understand the mechanisms of antibiotic resistance and the modifications in inflammatory cytokine dynamics, in order to develop immune boosters and surrogate immune biomarkers.

1.5. Effects on the Hematologic System

During short-duration spaceflight, the plasma volume and total blood volume de-crease within the first hours and remain reduced throughout the inflight period, a finding previously identified as space anemia [ 166 ]. Space anemia during spaceflight is perhaps due to a normal physiologic adaptation of newly released blood cells and iron metabolism to microgravity [ 167 ].

During long-duration spaceflight, microgravity exposure could potentially induce hemoglobin degradation, leading to hemolytic anemia. In a recent study of 14 astronauts who were on 6-month missions onboard the ISS, a 54% increase in hemolysis was ob-served after landing one year later [ 50 ]. In another small study, nearly half of astronauts (48%) landing after long duration missions were anemic and hemoglobin levels were characterized as having a dose–response relationship with microgravity exposure [ 51 ]. An additional study collected whole blood sample from astronauts during and after up to 6 months of orbital spaceflight [ 168 ]. Upon analysis, once the astronauts returned to Earth RBC and hemoglobin levels were significantly elevated. It is worth noting that these studies analyzed blood samples from astronauts collected after spaceflight, which may be influenced by various factors (e.g., the stress of landing and re-adaptation to conditions on Earth). In addition, these studies may be confounded by other extraterrestrial environmental factors such as fluid shifts, dehydration, and alteration of the circadian cycle.

Further research is urgently needed to understand plasma volume physiology dur-ing spaceflight and delineate the etiology and degree of hemolysis with longer space exposure, such as 1-year ISS or Mars exploration missions.

1.6. Oncologic Effects

Even during short-duration spaceflight, the stochastic nature of cancer development makes it possible that space radiation exposure could cause cancer via epigenomic modifications [ 63 ]. Currently, our epidemiological understanding of radiation-induced cancer risk is based primarily on atomic bomb survivors and accidental radiation exposures, which both show a clear association between radiation exposure and cancer risk [ 169 , 170 ]. However, these studies are hard to generalize to spaceflight as the patient populations vary significantly (generally healthy astronauts vs. atomic bomb survivors [NCRP 126]) [ 171 ]. Moreover, the radiation encountered in space is notably different than that associated with atomic bomb exposure. Most terrestrial exposures are based on low LET radiation (e.g., atomic bomb survivors received <1% dose from high LET neutrons) [ 172 ], whereas space radiation is comprised of higher LET ions (solar energetic particles and galactic cosmic rays) [ 173 , 174 ].

During long-duration spaceflight, our current understanding of cancer risk is also largely unknown. Our current epidemiologic understanding of long-duration radiation exposure and cancer risk is primarily based on the study of chronic occupational exposures and medically exposed individuals, supplemented with data obtained from animal studies, which are again based overwhelmingly on low LET radiation [ 169 , 170 , 175 , 176 ]. In animal studies, exposure to ionizing radiation (up to 13.5 months) has been associated with an increased risk of developing a variety of cancers [ 162 , 177 , 178 , 179 , 180 ]. Ionizing radiation exposure may cause DNA methylation patterns similar to the specific patterns observed in human adenocarcinomas and squamous cell carcinomas [ 63 ]; however, this response is not yet certain [ 181 , 182 ].

For the purposes of risk prediction, the elevated biological potency of heavy ions is modeled through concepts such as the radiation weighting factor, with NASA recently releasing unique quality factors ( Q NASA ) focused on high density tracks [ 183 ]. Although these predictive models can only estimate the impact of radiation exposure, extrapolation of current terrestrial-based data suggest that this risk could be at least substantial for astronauts. NASA, for example, has updated crew permissible career exposure limits to 0.6Sv, independent of age and sex. This degree of exposure results in a 2–3% mean increased risk of death from radiation carcinogenesis (NCRP 2021) [ 184 ]. This limit would be reached between 200 and 400 days of space travel (depending on degree of radiation shielding) [ 48 ].

Further research is urgently needed to understand the true risk of space radiation exposure. This is especially important for individuals with certain genotype-phenotype profiles (e.g., BRCA1 or DNA methylation signatures) who may be more sensitive to the effects of radiation exposure. Most importantly, the utilization of genotype-phenotype profiles of astronauts or space travelers is valuable not just for pre-flight screening, but also during in-flight travel, especially for long-duration flights to deeper space. An individual’s genetic makeup will in-variably change during spaceflight due to the shifting epigenetic microenvironment. Future crewed-missions to deep space will have to adapt to these anticipated changes, be-come aware of impending red-flag situations, and determine whether any meaningful shift or change to ones’ genetic makeup is possible. For example, personalized radiation shields could potentially be tailored to an individuals’ genotype-phenotype profile, individualized pulmonary capillary wedge pressure under microgravity may be different due to transient changes in left atrial structure, or preflight analysis of the globin gene for the prediction of space anemia [ 50 , 129 , 185 ]. This research should be designed to identify the radiation type, dose, quality, frequency, and duration of exposure required for cancer development.

1.7. Effects on the Neurologic System

During the initial days of spaceflight, space motion sickness (SMS) is the most commonly encountered neurologic condition. Microgravity exposure during spaceflight commonly leads to alterations in spatial orientation and gaze stabilization (e.g., shape recognition [ 186 ], depth perception and distance [ 187 , 188 ]). Postflight, impairments in object localization during pitch and roll head movements [ 189 , 190 ] and fine motor control (e.g., force modulation [ 191 ], keyed pegboard completion time [ 192 ], and bimanual coordination [ 193 ]) are common. Anecdotally, astronauts also reported alterations in smell and taste sensations during their missions [ 27 , 194 , 195 ]. The observed impairment in olfactory function is perhaps due to elevated intracranial pressure (ICP) with increased cerebrospinal fluid outflow along the cribriform plate pathways [ 196 ]. However, to date, there have been no studies directly measuring ICP during spaceflight.

Upon returning from spaceflight, studies have observed that astronauts experience decrements in postural and locomotor control that can increase fall risk [ 197 ]. These decrements have been observed in both standard sensorimotor testing and functional tasks. While recovery of sensorimotor function occurs rapidly following short-duration spaceflight (within the first several days after return) [ 192 , 198 ], recovery after long-duration spaceflight often takes several weeks. Similar to SMS, post-flight motion sickness (PFMS) is very common and occurs soon after g-transition [ 30 ]. Deficits in dexterity, dual-tasking, and vehicle operation [ 199 ] are also commonly observed immediately after spaceflight. Therefore, short-duration astronauts are recommended to not drive automobiles for several days, and only after a sensorimotor evaluation (similar to a field sobriety test).

Similarly to the effects seen following short-duration spaceflight, those returning from long-duration spaceflight can also experience deficits in dexterity, dual-tasking, and vehicle operation. Long-duration astronauts are recommended to not drive automobiles for several weeks, and also require a sensorimotor evaluation. While central nervous system (CNS) changes [ 53 ] associated with long-duration spaceflight are commonly observed, the resulting effects of these changes both during and immediately after spaceflight remain unclear [ 199 ]. Observed CNS changes include structural and functional alterations (e.g., upward shift of the brain within the skull [ 54 ], disrupted white matter structural connectivity [ 55 ], increased fluid volumes [ 56 ], and increased cerebral vasoconstriction [ 200 ]), as well as modifications to adaptive plasticity [ 53 ]. Adaptive reorganization is primarily observed in the sensory systems. For example, changes in functional connectivity during plantar stimulation have been observed within sensorimotor, visual, somatosensory, and vestibular networks after spaceflight [ 201 ]. In addition, functional responses to vestibular stimulation were altered after spaceflight―reducing the typical deactivation of somatosensory and visual cortices [ 202 ]. These studies provide evidence for sensory reweighting among visual, vestibular, and somatosensory inputs.

Further research is required to fully understand the observed CNS changes. In addition, integrated countermeasures are needed for the acute effects of g-transitions on sensorimotor and vestibular function.

1.7.1. Effects on the Neuro-Ocular System

Prolonged exposure to ionizing radiation is well known to produce secondary cataracts [ 61 , 62 ]. Most importantly, Spaceflight Associated Neuro-Ocular Syndrome (SANS) is a unique constellation of clinical and imaging findings which occur to astronauts both during and after spaceflight, and is characterized by: hyperopic refractive changes (axial hyperopia), optic disc edema, posterior globe flattening, choroidal folds, and cotton wool spots [ 43 ]. Ophthalmologic screening for SANS, including both clinical and imaging assessments is recommended. ( Figure 2 ) Although the precise etiology and mechanism for SANS remain ill-defined, some proposed risk factors for the development of SANS include microgravity related cephalad fluid shifts [ 203 ], rigorous resistive exercise [ 204 ], increased body weight [ 205 ], and disturbances to one carbon metabolic pathways [ 206 ]. Many scientists believe that the cephalad fluid shift secondary to microgravity exposure is the major pathophysiological driver of SANS [ 203 ]. Although inflight lumbar puncture has not been attempted, several mildly elevated ICPs have been recorded in astronauts with SANS manifestations upon returning to Earth [ 43 ]. Moreover, changes to the pressure gradient between the intraocular pressure (IOP) and ICP (the translaminar gradient) have been proposed as a pathogenic mechanism for SANS [ 207 ]. The translaminar gradient may explain the structural changes seen in the posterior globe such as globe flattening and choroidal folds [ 207 ]. Alternatively, the microgravity induced cephalad fluid shift may impair venous or cerebrospinal drainage from the cranial cavity and/or the eye/orbit (e.g., choroid or optic nerve sheath). Impairment of the glymphatic system has also been proposed as a contributing mechanism to SANS, but this remains unproven [ 208 , 209 ]. Although permanent visual loss has not been observed in astronauts with SANS, some structural changes (e.g., posterior globe flattening) may persist and have been documented to remain for up to 7 years of long-term follow-up [ 210 ]. Further research is required to better understand the mechanism of SANS, and to develop effective countermeasures prior to longer duration space missions.

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Ophthalmologic screening for SANS.

1.7.2. Effects on the Neuro-Behavioral System

The combination of mission-associated stressors with the underlying confinement and social isolation of space travel has the potential to lead to cognitive deficits and the development of psychiatric disorders [ 211 ]. Examples of previously identified cognitive deficits associated with spaceflight include impaired concentration, short-term memory loss, and an inability to multi-task. These findings are most evident during G-transitions, and are likely due to interactions between vestibular and cognitive function [ 212 , 213 ]. Sopite syndrome, a neurologic component of motion sickness, may account for some cognitive slowing. The term “space fog”, has been used to describe the generalized lack of focus, altered perception of time, and cognitive impairments associated with spaceflight, which can occur throughout the mission. This may be related to chronic sleep deprivation as deficiencies (including decreased sleep duration and quality of sleep) are prevalent despite the frequent use of sleep medications [ 71 ]. These results highlight the broad impact of space travel on cognitive and behavioral health, and support the need for integrated countermeasures for long-duration explorative missions.

1.8. Effects on the Musculoskeletal System

During short-duration spaceflight, low back pain and disk herniation are common due to the presence of microgravity. While the pathogenesis of space-related low back pain and disk herniation is complex, the etiology is likely multifactorial in nature (e.g., microgravity induced hydration and swelling of the vertebral disk, muscle atrophy of the neck and lower back) [ 19 , 214 , 215 ]. Additionally, various joint injuries (e.g., space-suited shoulder injuries) can also occur in space due to the presence of microgravity [ 16 , 216 , 217 , 218 ]. Interestingly, one study showed that performing specific exercises could potentially promote automatic and tonic activation of lumbar multifidus and transversus abdominis as well as prevent normal lumbopelvic positioning against gravity following bed rest as a simulation of space flight [ 219 ], and the European Space Agency suggested that exercise program could relieve low back pain during spaceflight [ 220 ]. Further longitudinal studies are required to develop specialized exercise protocols during space travel.

During long-duration spaceflight, the presence of microgravity could cause an alteration in collagen fiber orientation within tendons, reduce articular cartilage and meniscal glycosaminoglycan content, and impair the wound healing process [ 22 , 23 , 24 , 221 ]. These findings seen in animal studies suggest that mechanical loading is required in order for these processes to occur in a physiologic manner. It is theorized that there is a mandatory threshold of skeletal loading necessary to direct balanced bone formation and resorption during healthy bone remodeling [ 222 , 223 ]. Despite the current countermeasure programs, the issue of skeletal integrity is still not solved [ 224 , 225 , 226 ].

Space radiation could also impact bone remodeling, though the net effect differs based on the amount of radiation involved [ 6 ]. In summary, high doses of space radiation lead to bone destruction with increased bone resorption and reduced bone formation, while low doses of space radiation actually have a positive impact with increased mineralization and reduced bone resorption. Most importantly, space radiation, particularly solar particle events in the case of a flare, may induce acute radiation effects, leading to hematopoietic syndrome [ 7 ]. This risk is highest for longer duration missions, but can be substantially minimized with current spacecraft shielding options.

Longitudinal studies are required to develop special exercise protocols and further assess the aforementioned risk of space radiation on the development of musculoskeletal malignancies.

1.9. Effects on the Pulmonary System

During short-duration spaceflight, a host of changes to normal, physiologic pulmonary function have been observed [ 73 , 227 ]. Studies during parabolic flight have shown that the diaphragm and abdomen are displaced cranially due to microgravity, which is accompanied by an increase in the diameter of the lower rib cage with outward movement. Due to the observed changes to the shape of the chest wall, diaphragm, and abdomen, alterations to the pressure-volume curve resulted in a net reduction in lung volumes [ 228 ]. In five subjects who underwent 25 s of microgravity exposure during parabolic flight, functional residual capacity (FRC) and vital capacity (VC) were found to be reduced [ 229 ]. During the Spacelab Life Sciences-1 mission, microgravity exposure resulted in 10%, 15%, 10–20%, and 18% reductions in VC, FRC, expiratory reserve volume (ERV), and residual volume (RV), respectively, compared to values seen in Earth’s gravity [ 227 ]. The observed physiologic change in FRC is primarily due to the cranial shift of the diaphragm and abdominal contents described previously, and secondarily to an increase in intra-thoracic blood volume and more uniform alveolar expansion [ 227 ].

One surrogate measure for the inhomogeneity of pulmonary perfusion can be assessed through changes in cardiogenic oscillations of CO 2 (oscillations in exhaled gas composition due to differential flows from different lung regions with differing gas composition). Following exposure to microgravity, the size of cardiogenic oscillations were significantly reduced to 60% in comparison to the preflight standing values [ 230 , 231 ]. Possible causes of the observed inhomogeneity of ventilation include regional differences in lung compliance, airway resistance, and variations in motion of the chest wall and diaphragm. Access to arterial blood gas analysis would allow for enhanced physiologic evaluations, as well as improved management of clinical emergencies (e.g., pulmonary embolism) occurring during space travel. However, there is currently no suitable method for assessing arterial blood in space. The earlobe arterialized blood technique for collecting blood gas has been proposed, but evidence is limited [ 232 ]. Further research is required in this area to establish an effective means for sampling arterial blood during spaceflight.

In comparison to the changes seen during short-duration spaceflight, studies conducted during long-duration spaceflight showed that the heterogeneity of ventilation/perfusion (V/Q) was largely unchanged, with preserved gas exchange, VC, and respiratory muscle strength [ 73 , 233 , 234 ]. This resulted in overall normal lung function. This is supported by long-duration studies (up to 6 months) in microgravity which demonstrated that the function of the normal human lungs is largely unchanged following the removal of gravity [ 233 , 234 ]. It is worth noting that there were some small changes which were observed (e.g., an increase in ERV in the standing posture) following long-duration spaceflight, which can perhaps be attributed to a reduction in circulating blood volume [ 233 , 234 ]. However, while microgravity can causes temporary changes in lung function, these changes were reversible upon return to Earth’s gravity (even after 6 months of exposure to microgravity). Based on the currently available data, the overall effect of acute and sustained exposure to microgravity does not appear to cause any deleterious effects to gas exchange in the lungs. However, the biggest challenge for long-duration spaceflight is perhaps extraterrestrial dust exposure. Further research is required to identify the long term consequences of extraterrestrial dust exposure and develop potential countermeasures (e.g., specialized face masks) [ 73 ].

1.10. Effects on the Dermatologic System

During short-duration space travel, skin conditions such as contact dermatitis, skin sensitivity, biosensor electrolyte paste reactions, and thinning skin are common [ 44 , 235 ]. However, these conditions are generally mild and unlikely to significantly impact astronaut safety or prevent completion of space missions [ 44 ].

The greatest dermatologic concern for long-duration space travelers is the theoretical increased risk of developing skin cancer due to space radiation exposure. This hypothesis is supported by one study which found the rate of basal cell carcinoma, melanoma, and squamous cell carcinoma of the skin to be higher among astronauts compared to a matched cohort [ 236 ]. While the three-fold increase in prevalence was significant, there were a number of confounders (e.g., the duration of prolonged UV exposure on Earth for training or recreation, prior use of sunscreen protection, genetic predisposition, and variations in immune system function) that must also be taken into account. A potential management strategy for dealing with various skin cancers during space travel involves telediagnostic and telesurgical procedures. Further research is needed to improve the telediagnosis and management of dermatological conditions (e.g., adjustment for a lag in communication time) during spaceflight.

1.11. Diagnostic Imaging Modalities in Space

In addition to routine physical examination, various medical imaging modalities may be required to monitor and diagnose medical conditions during long-duration space travel. To date, ultrasound imaging acquired on space stations has proven to be helpful in diagnosing a wide array of medical conditions, including venous thrombosis, renal and biliary stones, and decompression sickness [ 29 , 237 , 238 , 239 , 240 , 241 , 242 ]. Moreover, the Focused Assessment with Sonography for Trauma (FAST), utilized by physicians to rapidly evaluate trauma patients, may be employed during space missions to rule out life-threatening intra-abdominal, intra-thoracic, or intra-ocular pathology [ 243 ]. Remote telementored ultrasound (aka tele-ultrasound) has been previously investigated during the NASA Extreme Environment Missions Operations (NEEMO) expeditions [ 244 ]. Today, the Butterfly iQ portable ultrasound probe can be linked directly to a smartphone through cloud computing, allowing physicians/specialists to promptly analyze remote ultrasound images [ 245 ].

Currently, alternative imaging modalities such as X-ray, CT, PET and MRI scan are unable to be used in space due to substantial limitations (e.g., limited space for large imaging structures, difficulties in interpretation due to microgravity). However, it is possible that the future development of a photocathode-based X-ray source may one day make this a possibility [ 101 , 246 ]. If X-ray imaging was possible, certain caveats would need to be taken into account for accurate interpretation. For example, pleural effusions, air-fluid levels, and pulmonary cephalization commonly seen on terrestrial imaging, would need to be interpreted in an entirely different way due to the effect of microgravity [ 247 ]. While this adjustment might be challenging, the altered principles of weightless physiology may provide some advantages as well. For example, one study found that intra-abdominal fluid was better able to be detected in space than in the terrestrial environment due to gravitational alterations in fluid dynamics [ 248 ]. Further research is required to identify and optimize inflight imaging modalities for the detection and treatment of various medical conditions.

1.12. Medical and Surgical Procedures in Space

Despite the presence of microgravity, both basic life support and advanced cardiac life support are feasible during space travel with some modifications [ 249 , 250 ]. For example, the recent guidelines for CPR in microgravity recommend specialized techniques for delivering chest compressions [ 251 ]. The use of mechanical ventilators, and moderate sedation or general anesthesia in microgravity are also possible but the evidence is extremely limited [ 252 , 253 ]. In addition, there are several procedures such as endotracheal intubation, percutaneous tracheostomy, diagnostic peritoneal lavage, chest tube insertion, and advanced vascular access which have only been studied through artificial stimulation [ 254 , 255 ].

Once traditionally “surgical” conditions are appropriately diagnosed, the next step is to determine whether these conditions should be managed medically, percutaneously, or surgically (laparoscopic vs. open procedures) [ 47 , 256 ]. For example, acute appendicitis or cholecystitis that would historically be managed surgically in terrestrial hospitals, could instead be managed with antibiotics rather than surgery. While the use of antibiotics for these conditions is usually effective on Earth, there remain concerns due to space-induced immune alterations, increased pathogenicity and virulence of microorganisms, and limited resources to “rescue” cases of antibiotic failure [ 39 ]. In cases of antibiotic failure, one potential minimally invasive option could be ultrasound-guided percutaneous drainage, which has previously been demonstrated to be possible and effective in microgravity [ 257 ]. Another potential approach is to focus on the early diagnosis and minimally invasive treatment of appropriate conditions, rather than treating late stage disease. In addition to expediting the patient’s post-operative recovery, minimally invasive surgery in space has the added benefit of protecting the cabin environment and the remainder of the crew [ 258 , 259 ].

As in all aspects of healthcare delivery in space, the presence of microgravity can complicate even the most basic of procedures. However, based on collective experience to date, if the patient, operators, and all required equipment are restrained, the flow of surgical procedures remains relatively unchanged compared to the traditional, terrestrial experience [ 260 ]. A recent animal study confirmed that it was possible to perform minor surgical procedures (e.g., vessel and wound closures) in microgravity [ 261 ]. Similar study during parabolic flight has further confirmed that emergent surgery for the purpose of “damage control” in catastrophic scenarios can be conducted in microgravity [ 262 ]. As discussed previously, telesurgery may be feasible if the surgery can be performed with an acceptably brief time lag (<200 ms) and if the patient is within a low Earth orbit [ 263 , 264 ]. However, further research and technological advancements are required for this to come to fruition.

1.13. Lifestyle Management in Space

Based on microgravity simulation studies, NASA has proposed several potential biomedical countermeasures in space [ 33 , 160 , 161 ]. Mandatory exercise protocols in space are crucial and can be used to maintain physical fitness and counteract the effects of microgravity. While these protocols may be beneficial, exercise alone may not be enough to prevent certain effects of microgravity (e.g., an increase in arterial thickness/stiffness) [ 20 , 265 , 266 , 267 ]. For example, a recent study found that resistive exercise alone could not suppress the increase in bone resorption that occurs in space [ 20 ]. Hence, a combination of resistance training and an antiresorptive medication (e.g., bisphosphonate) appears to be optimal for promotion of bone health [ 20 , 21 ]. Further research is needed to identify the optimal exercise regimen including recommended exercises, duration, and frequency.

In addition to exercise, dietary modification may be another potential area for optimization. The use of a diet based on caloric restriction (CR) in space remains up for debate. Based on data from terrestrial studies, caloric restriction may be useful for improving vascular health; however, this benefit may be offset by the associated muscle atrophy and osteoporosis [ 268 , 269 ]. Given that NASA encourages astronauts to consume adequate energy to maintain body mass, there has been an attempt to mimic the positive effects of CR on vascular health while providing appropriate nutrition. Further research is needed this area to identify the ideal space diet.

Based on current guidelines, only vitamin D supplementation during space travel is recommended. Supplementation of A, B6, B12, C, E, K, Biotin, folic acid are not generally recommended at this time due to insufficient evidence [ 64 ] ( Table S3 ). The use of traditional prescription medications may not function as intended on Earth. Therefore, alternative methods such as synthetic biologic agents or probiotics may be considered [ 35 , 38 ]. However, evidence in this area is extremely limited, and it is possible that the synthetic agents or probiotics may themselves be altered due to microgravity and radiation exposure. Further research is needed to investigate the relationship between these supplements and potential health benefits in space.

Currently, most countermeasures are directed towards cardiovascular system and musculoskeletal pathologies but there is little data against issues like immune and sleep deprivation, SANS, skin, etc. Artificial Gravity (AG) has been postulated as adequate multi-system countermeasure especially the chronic exposure in a large radius systems. Previously, the main barrier is the huge increase in costs [ 270 , 271 , 272 ]. However, there are various studies that show the opposite and also the recent decrease in launch cost makes the budget issue nearly irrelevant especially when a huge effort is paid to counteract the lack of gravity. The use of AG especially long-radius chronic AG is feasible. Further studies are needed to determine the utilization of AG in long-duration space travel.

1.14. Future Directions for Precision Space Health with AI

In this new era of space travel and exploration, ‘future’ tools and novel applications are needed in order to prepare deep space missions, particularly pertaining to strategies for mitigating extraterrestrial environmental factors, including both exogenous and en-dogenous processes. Such ‘future’ tools could help assist and ensure a safe travel to deep space, and more importantly, help bring space travelers and astronauts back to Earth. These tools and methods may initially be ‘remotely’ controlled, or have its data sent back to Earth for analysis. Primarily efforts should be focused on analyzing data in situ, and on site during the mission itself, both for the purpose of efficiency, and for the progressive purpose of slowly weaning off a dependency on Earth.

AI is an emerging tool in the big data era and AI is considered a critical aspect of ‘fu-ture’ tools within the healthcare and life science fields. A combination of AI and big data can be used for the purposes of decision making, data analysis and outcome prediction. Just recently, there have been encourage in advancements in AI and space technologies. To date, AI has been employed by astronauts for the purpose of space exploration; however, we may just be scratching the surface of AI’s potential. In the area of medical research, AI technology can be leveraged for the enhancement of telehealth delivery, improvement of predictive accuracy and mitigation of health risks, and performance of diagnostic and interventional tasks [ 273 ]. The AI model can then be trained and have its inference leveraged through cloud computing or Edge TPU or NVIDIA Jetson Nano located on space stations. ( Table 3 and Table S4 ) Figure 3 demonstrates potential AI applications in space.

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Potential AI applications in space.

As described previously, the capability to provide telemedicine beyond LEO is primarily limited by the inability to effectively communicate between space and Earth in real-time [ 274 ]. However, AI integration may be able to bridge the gap and advance communication capabilities within the space environment [ 275 , 276 ]. One study demonstrated a potential mechanism for AI incorporation in which an AI-generated predictive algorithm displayed the projected motion of surgical tools to adjust for excess communication lag-time [ 277 ]. This discovery could potentially enable AI-enhanced robotics to complete repetitive, procedural tasks in space without human inputs (e.g., vascular access) [ 278 ]. Today, procedures performed with robotic assistance are not yet fully autonomous (they still require at least one human expert). It is possible with future iterations that an AI integration could be created with the ability to fully replicate the necessary human steps to make terrestrial procedures (e.g., percutaneous coronary intervention, incision and drainage [ 103 ], telecholecystectomy [ 105 , 106 ], etc.) feasible in space [ 275 , 279 ]. The seventh NEEMO mission previously demonstrated that robotic surgery controlled by a remote physician is feasible within the environment of a submarine, but it remains to be seen whether this can be expanded to the space environment [ 280 ].

On space stations, Edge TPU-accelerated AI inference could be used to generate accurate risk prediction models based on data obtained from simulated environments (e.g., NASA AI Risk Prediction Challenge) [ 281 ]. For example, AI could potentially utilize data (e.g., -omics) obtained from research conducted both on Earth and in simulated environments (e.g., NASA GCR Simulator) to predict an astronaut’s risk of developing cancer due to high-LET radiation exposure (cytogenetic damage, mitochondrial dysregulation, epigenetic alterations, etc.) [ 63 , 78 , 79 , 282 , 283 , 284 ].

Another potential area for AI application is through integration with wearable technology to assist in the monitoring and treatment of a variety of medical conditions. For example, within the field of cardiovascular medicine, wearable sensor technology has the capability to detect numerous biosignals including an individual’s cardiac output, blood pressure, and heart rate [ 285 ]. AI-based interpretation of this data can facilitate prompt diagnosis and treatment of congestive heart failure and arrhythmias [ 285 ]. In addition, several wearable devices in various stages of development are being created for the detection and treatment of a wide array of medical conditions (obstructive sleep apnea, deep vein thrombosis, SMS, etc.) [ 285 , 286 , 287 , 288 ].

As discussed previously, the confinement and social isolation associated with prolonged space travel can have a profound impact on an astronaut’s mental health [ 8 , 10 , 67 ]. AI-enhanced facial and voice recognition technology can be implemented to detect the early signs of depression or anxiety better than standardized screening questionnaires (e.g., PHQ-9, GAD-7) [ 68 , 69 ]. Therefore, telepsychology or telepsychiatry can be used pre-emptively for the diagnosis of mental illness [ 68 , 69 , 289 ].

2. Conclusions

Over the next decade, NASA, Russia, Europe, Canada, Japan, China, and a host of commercial space companies will continue to push the boundaries of space travel. Space exploration carries with it a great deal of risk from both known (e.g., ionizing radiation, microgravity) and unknown risk factors. Thus, there is an urgent need for expanded research to determine the true extent of the current limitations of long-term space travel and to develop potential applications and countermeasures for deep space exploration and colonization. Researchers must leverage emerging technology, such as AI, to advance our diagnostic capability and provide high-quality medical care within the space environment.

Acknowledgments

The authors would like to thank Tyson Brunstetter, (NASA Johnson Space Center, Houston, TX) for his suggestions and comments on this article as well as providing the update NASA’s SANS Evidence Report, Ajitkumar P Mulavara, (Neurosciences Laboratory, KBRwyle, Houston, TX), Jonathan Clark, (Neurology & Space Medicine, Center for Space Medicine, Houston, TX), Scott M. Smith, (Nutritional Biochemistry, Biomedical Research and Environmental Sciences Division, Human Health and Performance Directorate, NASA Johnson Space Center, Houston, TX) for his suggestions and providing the update NASA’s Nutrition Report, G. Kim Prisk, (Department of Medicine, Division of Physiology, University of California, San Diego, La Jolla, CA), Lisa C. Simonsen (NASA Langley Research Center, Hampton, VA), Siddharth Rajput, (Royal Australasian College of Surgeons, Australia and Aerospace Medical Association and Space Surgery Association, USA), David S. Martin, MS, (KBR, Houston, TX), ‪David W. Kaczka, (Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, Iowa), Benjamin D. Levine (Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, University of Texas Southwestern Medical Center), Afshin Beheshti (NASA Ames Research Center), Christopher Wilson (NASA Goddard Space Flight Center), Michael Lowry (NASA Ames Research Center), Graham Mackintosh (NASA Advanced Supercomputing Division), and staff from NASA Goddard Space Flight Center for their suggestions. In addition, the authors would like to thank the anonymous reviewers for their careful reading of our manuscript, constructive criticism, and insightful comments and suggestions.

Abbreviations

Supplementary materials.

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cells12010040/s1 , Table S1: title Summary of gut microbial alteration during spaceflight; Table S2: title Summary of immune/cytokine changes during spaceflight; Table S3: title Summary of diet recommendation during spaceflight; Table S4: title Summary of AI technology and potential applications in space.

Funding Statement

This research received no external funding.

Conflicts of Interest

Krittanawong discloses the following relationships-Member of the American College of Cardiology Solution Set Oversight Committee, the American Heart Association Committee of the Council on Genomic and Precision Medicine, the American College of Cardiology/American Heart Association (ACC/AHA) Joint Committee on Clinical Data Standards (Joint Committee), and the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Performance Measures, The Lancet Digital Health (Advisory Board), European Heart Journal Digital Health (Editorial board), Journal of the American Heart Association (Editorial board), JACC: Asia (Section Editor), and The Journal of Scientific Innovation in Medicine (Associate Editor). Other authors have no disclosure.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

March 22, 2023

Health Research Is Needed Now before Sending Civilians to Space

Now is the time to protect the health and safety of civilians who will be traveling, living and working in the dangerous environment of space

By Michael Marge

Blue Origin’s New Shepard lifts off from the Launch Site One launch pad carrying Good Morning America co-anchor Michael Strahan, Laura Shepard Churchley, daughter of astronaut Alan Shepard, and four other civilians on December 11, 2021 near Van Horn, Texas. The six are riding aboard mission NS-19, the third human spaceflight for the company which is owned by Amazon founder Jeff Bezos.

Mario Tama/Getty Images

Within decades, hundreds and perhaps thousands of average civilians will travel, live and work in space . Along with their space suits, they will bring with them their illnesses, chronic health problems and disabilities.

That changes the space story because until recently, career astronauts have been the only travelers in space, aside from the infrequent space tourist . But now that new space businesses are launching , the travelers and workers will be mostly civilians.

This civilian move into space has already started. Ticket-buying or privately funded passengers have traveled into suborbital space, 50 to 60 miles above Earth, during the past couple of years, courtesy of “New Space” firms Blue Origin and Virgin Galactic. In September 2021, billionaire Jared Isaacman rented Elon Musk’s Crew Dragon Resilience spaceship to carry him and three other civilians on a three-day journey around the Earth. Even without scientific evidence about health risks of such travel, Isaacman and Musk are willing to push the envelope further: They plan another flight this year called Polaris Dawn that would carry a private crew of four to the highest Earth orbit ever flown; the flight will include a spacewalk, one of space’s most hazardous endeavors. In addition, NASA has awarded incentive grants to three space corporations to build commercial orbital platforms that will start operating by the end of this decade. These space stations will be occupied by civilians as tourists and employees.

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We need to go the extra mile to protect civilians if they are to travel, live and work in space.

NASA’s reports on astronauts before, during and after extended space travel and habitation make this clear : astronauts face chronic motion sickness, neurological disorders, cardiovascular problems, increased risk for blood clotting and vision problems, as well as increased risks of cancer, muscle atrophy and bone loss. That’s despite their excellent health, physical and mental fitness, and years of training. As astronauts, they are fully aware of these risks and willing to take them. As former astronaut and now Senator Mark Kelly once said, “Being an astronaut is a high-risk job.” But average civilians in space should not take such risks, which for them are even more real.

In 2022, the CDC reported that within the U.S. population six in 10 adults have chronic disease , and four in 10 have two or more chronic diseases. Also, one in four have disabilities . These health conditions add a new and challenging dimension to space hazards on the human body. What we have learned from NASA is that the health profiles of astronauts and the health profiles of civilians are notably different.

To get ahead of this problem, a landmark scientific meeting was hosted in 2021 by the Commercial Spaceflight Federation (CSF) with the blessings of the National Space Council. Intended to develop the first ever “Human Research Program for Civilians in the Commercialization of Space,” a workshop of 100 experts, which I co-chaired, identified high-priority human research projects to safeguard civilians in space.

Unfortunately, some of the commercial space companies behind the health research program now appear uninterested. Why the turnaround? We can only speculate, but a host of answers suggest themselves, starting with the space industry hoping to retain a 2004 decision by Congress that imposed a moratorium on new safety regulations on human spaceflight , in the absence of death, serious injury or close call ; this “learning period,” which has been extended several times, gives the industry considerable leeway to experiment with humans. Second, these space companies compete with one another and are in a hurry to realize breakthroughs for their own business without slowing down for safety research. Third, some of the leaders in these companies challenge the cautions about the fragility of civilians in space. They argue that the hazards will have minor or short-term health impact. SpaceX CEO Elon Musk referred to the Inspiration4 spaceflight as “an intense roller coaster ride,” and added that anyone who can tolerate that “should be fine for flying on Dragon,” Musk’s spaceship. Some in the industry prefer to place average civilians in spaceflight, study them during and after flight and then examine ways to protect civilians in future flights. This risk-ridden exploratory approach to discovery should be discouraged. It returns us to the days of the Wright brothers (who had multiple crashes and the first air passenger death ), where discovery occurs by risking calamity.

If there is a catastrophic event where civilians become seriously ill, injured or die, only then will we wake up to the proposition that humans in space should travel without harm. Only then will we realize that the best approach is to conduct an unbiased, objective, large-scale, scientific human research program against all the known risks of space travel.

But given today’s space-race realities, here’s a compromise: While space companies prosper under the moratorium, let them send civilians into space only after each one has undergone a thorough physical, mental and performance examination and preparatory training comparable to what is required of NASA’s career astronauts. Each company should publicize its preflight health and performance testing and training program. In addition, the space industry should publicly support the human research program it originally endorsed. Taking these steps would send civilians into space in the coming months and years in a responsible and safe manner. It would benefit the industry, assure public trust, and help protect civilians in space.

Even without industry support, we need health research now to protect future civilians in space, under the Federal Aviation Administration’s Office of Space Transportation (AST), Federal Aviation Agency. The AST has the experience, the mission, expertise and organizational setup to do an exceptional job.

The time to act is now by asking the Biden administration and Congress to fund a program of human research for civilians in space before it is too late, and we learn once more that “guinea pig” discoveries are rarely happy ones.

This is an opinion and analysis article, and the views expressed by the author or authors are not necessarily those of Scientific American.

Keeping astronauts healthy in space isn’t easy − new training programs will prepare students to perform medicine while thousands of miles away from Earth

Emergency Medicine Physician, University of Colorado Anschutz Medical Campus

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A group of people wearing orange jumpsuits stand and talk while a man in blue jumpsuit lies on the ground.

In the coming decade, more people will go to space than ever before as human spaceflight enters a new era. NASA, the European Space Agency and other governmental agencies are partnering to develop crewed missions beyond the Moon. At the same time, these agencies are collaborating with private companies using new technologies to drive down the price of space exploration.

Companies such as SpaceX, Blue Origin and Sierra Space have developed vehicles with reusable boosters, automated flight systems and lightweight materials to support these deep space missions . Some even have ambitions of their own to build private space stations, Moon bases or mining operations in the coming decades.

But as these technologies and partnerships rapidly make spaceflight more accessible, new challenges emerge. For one, maintaining the health and performance of an astronaut crew. My team of researchers and educators at the University of Colorado and others around the world are looking to address this issue.

A group of people in orange jumpsuits stand around a table, with a person laying on it.

Emerging medical challenges in space

NASA astronauts are some of the most accomplished people on the planet, and they’re some of the healthiest. Astronauts undergo extensive medical and psychological testing that in one study disqualified 26% of final-round applicants . This rigorous screening and testing process effectively limits the chance of a medical event occurring during a mission.

But as spaceflight becomes more accessible, astronaut crews on commercial missions will likely make up the majority of space travelers in the coming years. Private missions will be short and stay in a close orbit around Earth in the near term, but private crews will likely have less training and more chronic medical conditions than the professional astronauts currently living and working in space.

While experiments aboard the International Space Station have extensively studied the normal physiological changes occurring to the human system in weightlessness, there is limited to no data about how common chronic diseases such as diabetes or high blood pressure behave in the space environment.

This industry boom is also creating opportunities for long-duration missions to the Moon and Mars. Because of the length of missions and the distance from Earth, professional astronauts on these missions will experience prolonged weightlessness, leading to bone and muscle loss, communication delays of a few seconds up to 40 minutes, and extreme isolation for months to years at a time.

Crews must function autonomously, while being exposed to new hazards such as lunar or Martian dust. Because of the fuel required for these missions, resources will be limited to the lowest mass and volume possible.

As a result, mission planners will need to make difficult decisions to determine what supplies are truly necessary in advance, with limited or unavailable resupply opportunities for food, water and medicine. In space, for example, radiation and humidity inside a spacecraft can cause medications to deteriorate more quickly and become unavailable or even toxic to crew members.

Crews on the space station have access to a flight surgeon at Mission Control to help manage medical care in the same way telehealth is used on Earth. Crews on distant planets, however, will need to perform medical care or procedures autonomously.

In the event of a medical emergency, crews may not be able to evacuate to Earth. Unlike the space station, where medical evacuations to Earth can occur in less than 24 hours, lunar evacuations may take weeks . Evacuations from Mars may not be possible for months or even years.

Put simply, the current approaches to medical care in spaceflight will not meet the needs of future commercial and professional astronauts. Researchers will need to develop new technologies and novel training approaches to prepare future providers to treat medical conditions in space.

The current leaders in space medicine are either experts in aerospace engineering or in medicine, but rarely do experts have formal training or a complete understanding of both fields. And these disciplines often can’t speak each other’s language both literally and figuratively.

Training the next generation

To meet the evolving demands of human spaceflight, educators and universities are looking to develop a way to train specialists who understand both the limitations of the human body and the constraints of engineering design.

Some schools and hospitals, such as the University of Texas Medical Branch , have residency training programs for medical school graduates in aerospace medicine. Others, such as UCLA and Massachusetts General Hospital , have specialty training programs in space medicine, but these currently target fully trained emergency medicine physicians.

My team at the University of Colorado has created a program that integrates human physiology and engineering principles to train medical students to think like engineers.

Two domed tents connected by long tubes, in the desert.

This program aims to help students understand human health and performance in the spaceflight environment. It approaches these topics from an engineering design and constraints perspective to find solutions to the challenges astronauts will face.

One of our most popular classes is called Mars in Simulated Surface Environments . This class puts students through engineering and medical scenarios in a simulated Mars environment in the Utah desert. Students deal with the challenges of working and providing care while wearing a spacesuit and on a desolate Mars-like landscape.

The stress of the simulations can feel real to the students, and they learn to apply their combined skill sets to care for their fellow crew members.

Educational programs like these and others aim to create cross-trained specialists who understand both patient care and the procedural nature of engineering design and can merge the two, whether for space tourists in orbit or as a pioneer to the surface of another planet.

A new period of spaceflight is here, and these programs are already training experts to make space accessible and safe.

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Impacts of space travel on astronauts' eye health

As space travel becomes more common, it is important to consider the impacts of space flight and altered gravity on the human body. Led by Dr. Ana Diaz Artiles, researchers at Texas A&M University are studying some of those impacts, specifically effects on the eye.

Gravitational changes experienced by astronauts during space travel can cause fluids within the body to shift. This can cause changes to the cardiovascular system, including vessels in and around the eyes.

As the commercialization of space flight becomes more common and individual space travel increases, astronauts will not be the only ones experiencing these changes. Individuals traveling to space with commercial companies may not be as fit or healthy as astronauts, making it even more important to understand the role that fluid shift plays in cardiovascular and eye health.

"When we experience microgravity conditions, we see changes in the cardiovascular system because gravity is not pulling down all these fluids as it typically does on Earth when we are in an upright position," said Diaz Artiles, an assistant professor in the Department of Aerospace Engineering and a Williams Brothers Construction Company Faculty Fellow. "When we're upright, a large part of our fluids are stored in our legs, but in microgravity we get a redistribution of fluids into the upper body."

These fluid shifts may be related to a phenomenon known as Spaceflight Associated Neuro-ocular Syndrome (SANS), which can cause astronauts to experience changes in eye shape and other ocular symptoms, such as changes in ocular perfusion pressure (OPP). At this time, researchers are unsure of the exact cause of SANS, but Diaz Artiles hopes to shed light on the underlying mechanism behind it.

Diaz Artiles and her team are investigating potential countermeasures to help counteract the headward fluid shifts of SANS. In a recent study, they examined the potential aid of lower body negative pressure (LBNP) to combat SANS. This countermeasure has the potential to counteract the effects of microgravity by pooling fluid back into the lower body.

While the role of ocular perfusion pressure in the development of SANS remains undetermined, Diaz Artiles and her team hypothesized that microgravity exposure could lead to a slight but chronic elevation (compared to upright postures) in OPP, which may have a role in the development of SANS. The results of the recently published study showed that lower body negative pressure, while effective in inducing fluid shift toward the lower body, was not an effective method for reducing OPP. Should elevated ocular perfusion pressure be definitively linked to SANS, the use of LBNP could theoretically not be an effective countermeasure to this syndrome. But they emphasize that future work should seek to better understand the relationship between OPP and SANS, and the impact of LBNP on these ocular responses as part of the countermeasure development.

"This research is just one experiment of a three-part study to better understand the effects of fluid shift in the body and its relationship to SANS. Previous experiments in this study included the use of a tilt table for researchers to understand the cardiovascular effects of fluid shifts at different altered gravity levels, recreated by using different tilt angles," said Diaz Artiles.

The published study, as well as upcoming research, focuses on countermeasures to the fluid shift; in this case, lower body negative pressure. In future studies, the researchers will examine the effects of using a centrifuge to combat the fluid shift and its effects. Diaz Artiles and her team aim to collect cardiovascular responses using each countermeasure and compare effects on ocular perfusion pressure and other cardiovascular functions that may be affected by microgravity environments. These studies are performed on Earth, so gravitational changes that occur in space may cause different outcomes. Thus, they hope to conduct future studies in true microgravity conditions, such as parabolic flights.

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Materials provided by Texas A&M University . Original written by Alyssa Schaechinger. Note: Content may be edited for style and length.

Journal Reference :

Eric A. Hall, Richard S. Whittle, Ana Diaz-Artiles. Ocular perfusion pressure is not reduced in response to lower body negative pressure . npj Microgravity , 2024; 10 (1) DOI: 10.1038/s41526-024-00404-5

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How does space travel affect eye health?

As space travel becomes more frequent, it is vital to consider the effects of space flight and altered gravity on human health.

Researchers at Texas A&M University , led by Dr. Ana Diaz Artiles, are focusing on the impact of microgravity conditions on human eye health.

Space travel and eye health

According to the scientists, fluid shifts caused by microgravity can affect the cardiovascular system, including eye vessels.

Spaceflight-Associated Neuro-ocular Syndrome

The microgravity changes can potentially lead to vision impairment, often referred to as Spaceflight-Associated Neuro-ocular Syndrome (SANS). This condition primarily affects astronauts who spend extended periods in microgravity environments.

SANS occurs when the fluid shifts associated with space travel increase pressure inside the skull and on the eyes, leading to changes in the shape of the eye and ocular perfusion pressure (OPP).

Symptoms of SANS

Common symptoms include swelling of the optic disc, flattening of the back of the eye (globe flattening), and changes in the retina. These changes can result in blurred vision, difficulties in focusing on near objects, and other visual distortions.

Mechanisms and countermeasures

The exact mechanisms behind SANS are still being studied, but it is clear that the prolonged exposure to microgravity plays a significant role.

Countermeasures such as special exercises, medications, and equipment like lower body negative pressure devices are being explored to mitigate these effects and protect astronauts' vision during long-duration space missions .

Fluid shifts during space flight

"When we're upright, a large part of our fluids are stored in our legs, but in microgravity, we get a redistribution of fluids into the upper body."

Mitigating headward fluid shifts

Dr. Diaz Artiles' team is exploring countermeasures like lower body negative pressure (LBNP) to mitigate headward fluid shifts.

The recent study found that while lower body negative pressure effectively moves fluids to the lower body, it does not reduce ocular perfusion pressure, suggesting it may not be an effective countermeasure for Spaceflight Associated Neuro-ocular Syndrome.

Further research is needed to fully understand the relationship between ocular perfusion pressure and SANS.

"This research is just one experiment of a three-part study to better understand the effects of fluid shift in the body and its relationship to SANS," said Dr. Diaz Artiles.

"Previous experiments in this study included the use of a tilt table for researchers to understand the cardiovascular effects of fluid shifts at different altered gravity levels, recreated by using different tilt angles."

Future research on space travel

Upcoming research will also aim to conduct experiments in true microgravity conditions, such as parabolic flights, to better understand the impact of space travel on the human body. This comprehensive approach aims to develop effective countermeasures for the health challenges posed by altered gravity environments in space.

"Concern over the accuracy of terrestrial LBNP experiments should be considered, as the combination of reduced central venous pressure while still experiencing G x (front-to-back) gravity conditions may produce results not necessarily comparable to physiological responses during spaceflight conditions. Thus, future studies should investigate LBNP responses in true microgravity conditions," noted the researchers.

Space travel and human health

Space travel significantly impacts the human body in various ways. The microgravity environment leads to muscle atrophy and bone density loss because the body doesn't have to support its weight.

Astronauts often experience fluid redistribution, causing puffy faces and thinner legs, as well as changes in cardiovascular function due to the shift of fluids toward the upper body. Vision can be affected, sometimes resulting in long-term impairment.

Additionally, space radiation poses a risk for increased cancer rates and potential damage to the nervous system. The psychological effects of isolation and confinement in space also present challenges, potentially leading to stress, sleep disorders, and other mental health issues.

Overall, the human body undergoes significant physiological and psychological stress during space travel, requiring extensive countermeasures and research to mitigate these effects.

The study is published in the journal NPJ Microgravity .

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Review Article
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Published: 11 June 2024

Understanding how space travel affects the female reproductive system to the Moon and beyond

Begum Mathyk ORCID: orcid.org/0000-0001-9832-6284 1 ,
Anthony N. Imudia 1 ,
Alexander M. Quaas ORCID: orcid.org/0000-0002-9644-2115 2 ,
Cihan Halicigil ORCID: orcid.org/0000-0003-1192-7832 3 ,
Fathi Karouia ORCID: orcid.org/0000-0002-1142-9684 4 , 5 , 6 , 7 ,
Pinar Avci na1 ,
Nicolas G. Nelson ORCID: orcid.org/0000-0001-9914-5637 8 ,
Ozlem Guzeloglu-Kayisli ORCID: orcid.org/0000-0001-5448-917X 9 ,
Miriah Denbo 9 ,
Lauren M. Sanders ORCID: orcid.org/0000-0001-9393-0861 10 , 11 ,
Ryan T. Scott ORCID: orcid.org/0000-0003-0654-5661 10 , 12 ,
Murat Basar ORCID: orcid.org/0000-0001-7766-409X 3 ,
Ana Paula Guevara-Cerdán ORCID: orcid.org/0009-0008-2134-1417 13 ,
Michael Strug ORCID: orcid.org/0000-0001-9784-889X 14 ,
Brent Monseur ORCID: orcid.org/0000-0002-9593-0766 14 ,
Umit A. Kayisli ORCID: orcid.org/0000-0002-0379-2168 9 ,
Nathaniel Szewczyk ORCID: orcid.org/0000-0003-4425-9746 15 ,
Christopher E. Mason ORCID: orcid.org/0000-0002-1850-1642 16 , 17 , 18 ,
Steven L. Young ORCID: orcid.org/0000-0002-5205-4495 19 ,
Savas Tasoglu ORCID: orcid.org/0000-0003-4604-217X 20 , 21 , 22 , 23 ,
Sylvain V. Costes ORCID: orcid.org/0000-0002-8542-2389 10 &
Afshin Beheshti ORCID: orcid.org/0000-0003-4643-531X 11 , 24

npj Women's Health volume 2 , Article number: 20 ( 2024 ) Cite this article

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Endocrine reproductive disorders
Reproductive biology

As the space industry grows exponentially and aspirations for space travel expand, we are entering a new era where we will very likely become an interplanetary species. Although reproduction is an essential human function and necessary for species survival, we have remarkably little knowledge regarding the impact of space travel on the female reproductive system. The effects of spaceflight on human reproductive potential, fertility, implantation and subsequent pregnancy resulting in a healthy live birth must be considered before planning prolonged spaceflight missions and the colonization of planets. In this review, we explore what is known and what remains to be learned about the effects of space travel on female reproductive endocrinology. We also delve deeper into reproductive endocrinology and discuss normal physiologic mechanisms at the molecular level to have a better understanding of how it may change during spaceflight. The rigors of spaceflight including radiation, gravitational stressors, and circadian rhythm changes could potentially affect ovulation, fertilization, endometrial receptivity, preimplantation embryo development, embryo implantation, placentation, and pregnancy. Thus, we will examine what is known about spaceflight effects on the hypothalamic–pituitary–gonadal (HPG) axis, ovarian folliculogenesis and steroidogenesis, early embryogenesis, endometrial receptivity, and pregnancy. We further discuss the recent advances in reproductive endocrinology and future research platforms. Establishing a better understanding of the effect of space travel on female reproductive health, as well as developing countermeasures to mitigate adverse effects, are decisive components of our species’ successful transition to an interplanetary one.

Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs

The maintenance of oocytes in the mammalian ovary involves extreme protein longevity

Underwater acoustic analysis reveals unique pressure signals associated with aircraft crashes in the sea: revisiting MH370

Introduction.

In 1969, Neil Armstrong famously said: “One small step for man, one giant leap for mankind.” Now, over 50 years later, the National Aeronautics and Space Administration (NASA) in collaboration with international partners is planning to return to the Moon with Artemis missions to establish a human habitat, land the first female on the Moon, and pave the way for future planetary missions in our solar system. With these early, but giant steps toward becoming an interplanetary species, we can no longer ignore potential reproductive challenges incurred during spaceflight and deep space exploration. Rather, we must identify and overcome (or accept) these challenges. The new NASA decadal survey marks a significant milestone in shaping the future of space research. It highlights the critical importance of understanding female biology in the next decade of NASA’s scientific endeavors 1 . The survey underscores the need for dedicated fundamental and applied research efforts to ensure the health, safety, and well-being of women during extended space missions by highlighting the physiologic complexities that female astronauts may face in space.

Since the first woman went to space, Valentina Tereshkova in 1963, the number of female astronauts has consistently increased along with the length of the mission. In the last decade, female astronauts went on longer-duration missions, lasting from 6 months to a year, far beyond the technical definition of long-duration flights (>30 days). With this increase in duration, comes longer exposure to the unique hazards and technical challenges of the space environment. Moreover, despite a significant increase in female crew assignments for the past few years, overall representation of women in spaceflight only represents 10% of total crewed missions.

During missions in low Earth orbit (LEO) and beyond, astronauts face identified risks such as space radiation, altered gravitational forces, circadian rhythm changes, isolation, communication delays, and limited health care access. These conditions are associated with oxidative stress, cancer, cardiac dysfunction, immune dysregulation, muscle atrophy, bone loss, limited nutrition, sleep disorders, and mood changes 2 . The “space exposome” is a unifying term, combining these space-related risk factors with individual factors such as age, gender, lifestyle, and genetics 3 . In the following sections, we will be discussing space-related risk factors and their impact on the female reproductive system. We provide insight on the physiology of reproductive endocrinology and possible pathophysiology that may occur during spaceflight based on current data.

Radiation exposure during spaceflight

One of the most studied space-related risk factors is exposure to ionizing radiation, which has been considered the main limiting factor for exploration class missions 4 . The geomagnetic field of the Earth primarily serves as a shield for life on our planet against charged particles present in galactic cosmic radiation 5 . Astronauts are considered as special radiation workers due to the unique space radiation environments of LEO and beyond 6 . NASA’s radiation exposure limits are set to maintain a 3% risk of exposure-induced death (REID) for cancer, using a 95% confidence level to address uncertainties in risk predictions 7 . This limit is based on age and sex-specific cancer risk assessments. This standard impose more lenient restrictions on men and older astronauts, whose cancer mortality risk attributable to radiation is presumed to be lower 8 . The National Academies released a report in 2021 that encouraged NASA to proceed with a universal standard corresponding to an estimated 3% cancer mortality risk increase for a 35-year-old female astronaut 4 . In early 2022, NASA adopted this new standard, limiting all astronauts to 600 mSv of radiation for their entire career 9 .

Unlike exposures to radiation on Earth, space radiation contains high-energy charged particles, including ions from solar flares (solar particle events; SPE) and galactic cosmic rays (GCR) from interstellar sources 10 . Aboard the International Space Station (ISS) in LEO, astronauts also encounter increased exposure to high-energy particles, particularly when the ISS passes through the South Atlantic Anomaly (SAA) with doses peaking several hundred µGy/min 11 . The SAA anomaly is a region where the Earth’s inner Van Allen Belt, which traps charged particles, comes closest to the Earth’s surface. Consequently, the ISS’s passage through this area results in heightened radiation levels. Therefore, the effective dose of galactic cosmic radiation for individuals on aircraft, is affected by factors like altitude, geographic location, the Earth’s magnetic field, and solar activity 12 . Cumulative exposures may be expected to be higher for crews of commercial spaceflight companies than airlines 13 . For example, total exposures aboard the ISS fluctuate around an equivalent 5–20 μGy per hour 14 , compared to an estimated 3.0–6.6 μGy per hour aboard international flights 15 .

The primary radiation risks for spaceflight crew beyond LEO are threefold: (1) Constant exposure to low-dose, low-energy solar wind; (2) Acute, sporadic, and somewhat unpredictable exposure to high-energy protons from Solar Particle Events (SPEs), originating from solar flares and Coronal Mass Ejections (CMEs); (3) Chronic low-dose exposure to high-energy Galactic Cosmic Rays (GCRs). GCRs include protons, helium ions, and heavier energetic elemental nuclei (HZE particles) accelerated by various celestial phenomena outside our solar system 16 . Notably, during solar minimum periods, SPEs become rarer, but the chronic dose rates from GCRs are about twice as high 14 . The intravehicular space radiation environment is further complicated by spallation, in which GCR collides with materials and triggers a cascade of nuclear fragmentation events that result in a shower of lower-energy ions and neutrons. As such, shielding cannot prevent exposure to GCR or the products of spallation 5 . The SPE that may threaten crew safety are mostly protons with kinetic energies of 50–300 MeV at high fluence. Exposure to SPE radiation decreases with thicker shielding, but contribution to generation of secondary neutrons from interaction with the shielding can increase exposure to radiation and it can pose a higher threat during extravehicular activities (EVA) 17 .

A distinction is made between sparsely ionizing (or low-linear energy transfer; low- LET) and densely ionizing (or high-LET) radiation. The LET of a particle is defined as the average energy deposited along its path per unit length, expressed in kiloelectron volts per micrometer (keV μm −1 ). Electromagnetic (photon) radiation, including X- and γ-rays, is considered low-LET because it deposits energy less densely along its track, depositing energy uniformly in the tissue. In contrast, α-particles and heavier energetic ions, which are critical components of the GCR, are densely ionizing (high-LET) because they deposit the majority of their energy along their linear trajectory 18 and can cause more complex DNA damage 19 and clustering of DNA double-strand breaks clustering 20 .

The proportion of GCR in space radiation will differ between the LEO and beyond-LEO environments, as well as the Martian surface 21 . The estimated total radiation dose received during a Mars mission, which typically includes 6 months of travel each way and an 18-month surface stay, is expected to result in a cumulative dose equivalent that is significantly lower than 1000 mGy 22 , 23 . This number is probably an under-estimation based on the recent radiation dosimeter readings during the cruise phase of the Mars Curiosity mission, which reported trans-Earth-Mars exposures of up to 1.8 mGy/day 24 or ~660 mGy for a 1-year travel alone, but could exceed 1200 mGy depending on trajectory, time of the mission, and stage of the solar cycle 25 . The total dose is also subject to change based on local conditions and extreme events such as solar flares.

The effect of radiation on female reproductive organs

Ionizing radiation damages DNA either directly or indirectly through reactive oxygen and nitrogen species 10 . The effects of acute radiation exposure can persist for years, as exemplified with high-LET radiation by persistent oxidative stress, lipid peroxidation, and mitochondrial dysfunction in the murine intestine one year after 56 Fe irradiation 26 . In turn, mitochondrial dysfunction and oxidative stress have been implicated in several diseases of the reproductive system as well as spaceflight pathologies 27 , 28 . For example, reactive oxygen species cause human endometrial endothelial cell apoptosis, thereby contributing to the pathogenesis of progestin contraceptive-mediated abnormal uterine bleeding 29 . Radiation exposure is also an independent risk factor for future cancer, and its potential association with gynecologic cancers during spaceflight has recently been reviewed 30 . Historically, most radiation studies have focused on the effects of acute radiation exposure, but recent efforts have also shifted to understanding the carcinogenic and tissue effects of chronic low-dose high-LET radiation, i.e., GCR 31 .

Our knowledge on the effects of radiation on the human body is largely derived from survivors of childhood cancer or atomic bombs, but there are important distinctions between clinical and environmental exposures. In external beam radiotherapy, high doses of targeted radiation are delivered to a specific anatomical region in discrete fractions. To suppress native bone marrow for stem cell transplantation, some patients receive total-body irradiation at a lower dose than radiotherapy but significantly higher than medical imaging. Regardless of dose and dose rate, these are all relatively brief, controlled exposures. On the other hand, environmental radiation results in more chronic, whole-body exposure, so one must be cautious when attempting to extrapolate data from one context to the other.

Radiation therapy has short and long-term reproductive toxicities that vary by total radiation dose as well as dose rate and radiation type (Table 1 ). Oocytes are exquisitely radiosensitive 32 , and radiotherapy is a known risk factor for primary ovarian insufficiency (POI) and premature menopause. Twelve-week-old C57BL/6J female mice, exposed to charged iron and oxygen particles in separate experiments conducted in the same laboratory, depletion of primordial follicles and estrous cycles irregularities were observed at different rates based on particle type and doses 33 , 34 , 35 . More specifically, the primordial follicle pool decreased by 71% after only 5 cGy of 600 MeV/n 18 O (16.5 keV/µm) exposure and was fully depleted following 30 cGy. In contrast, 57% follicle loss was observed after exposure to 5 cGy of 600 MeV/n 56 Fe (179 keV/µm) 33 . For the primordial follicle loss, the ED50 was 4.6 cGy and 27.5 cGy for oxygen and iron species, respectively 34 , indicating a differential effect based on ion species. These outcomes can be understood through Poisson statistics. Given the reported nuclear area of 113 µm 2 , a 5 cGy exposure implies that 88% of nuclei are likely to be hit by an oxygen particle and 18% by an iron particle. For oxygen, it’s estimated that 63% of nuclei experienced more than one hit, suggesting that two oxygen traversals might be necessary to destroy a follicle. Conversely, with iron particles, the mere 18% of nuclei hit by at least one particle reflects the higher Linear Energy Transfer (LET) of these particles, which release ~11 times more energy locally. This suggests that even a single traversal by an iron particle is sufficient for follicular destruction. The corresponding Poisson distribution target area for 57% hit by iron is ~500 µm 2 , meaning any particle impacting within this radius centered on a cell could be lethal.

In humans, ovarian damage after radiation is also dose- and age-dependent 36 (Table 1 ). Radiation-induced ovarian insufficiency and subsequent cessation of hormone production can lead to premature menopause and temporary or permanent infertility (Table 1 ). After radiotherapy, studies showed that an average of 2 Gy radiation can destroy half of human oocytes 37 , while POI occurs in 97% of women when exposed to 20.3 Gy at birth, 18.4 Gy at age 10 years and 14.3 Gy at age 30 years 36 . Therefore, a dose of 3.5–20 Gy can result in permanent infertility in women depending on their age (Table 1 ) 38 .

In addition to oocytes being radiosensitive, the larger organs that support fertilization and embryo development also show signs of damage when exposed to radiation. The vagina has mucosal layer, a radiosensitive tissue. Radiotherapy can cause mucosal atrophy and vaginal stenosis, resulting in dyspareunia and vaginal dryness 39 . The uterus is known to be more radioresistant than the ovaries, but changes in cervical length, endometrial thickness, and junctional zone visibility have been reported in colorectal cancer survivors after pelvic radiotherapy 40 . Furthermore, when females are exposed to pelvic irradiation at a young age, their uterine volumes are reported to be decreased in adulthood 41 . Uterine exposure to radiotherapy during childhood also increases the risk of pregnancy complications such as preterm delivery and low birth weight 42 . As for chronic low-dose exposure, one recent study found an association between higher levels of home radon, a radioactive gas, and the incidence of hypertensive disorders in pregnancy 43 .

Cranial radiotherapy affects the central nervous system, and the hypothalamic–pituitary–gonadal (HPG) axis is the central regulator of reproductive endocrinology (Fig. 1 ). The pituitary gland secretes follicle-stimulating hormone (FSH) and luteinizing-hormone (LH) along with other crucial hormones such as growth hormone, thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), prolactin, oxytocin, and vasopressin. Pituitary dysfunction has been reported in patients with brain and neck malignancies who underwent radiotherapy 44 . Radiation-induced pituitary dysfunction can be permanent and progressive, with effects dependent on pituitary cell type, radiation dose, age, and sex 45 . Moreover, cranial radiotherapy has been associated with gonadotropin alterations and can cause pubertal delay or precocious puberty 46 . Precocious puberty was reported after the administration of 30 Gy 45 .

This figure illustrates GnRH secretion, as well as the downstream effects of FSH and LH. It also shows the action of FSH and LH on gonads, and depicts the two-cell, two-gonadotropin model of estrogen synthesis.

Lastly, the dose threshold for radiation-induced teratogenesis during pregnancy differs based on the gestational age (Table 2 ). During early embryogenesis, radiation exposure results in an “all or none” phenomenon, but afterward the occurrence and degree of unwanted effects in the fetus often depend on the gestation and dose received (Table 2 ).

It is important to reemphasize that radiotherapy entails brief, acute, and targeted exposures at much higher dose rates than those experienced in LEO and beyond. Furthermore, differences in radiation quality can produce different biological responses. The existing research on radiation risks to the female reproductive system primarily relies on therapeutic doses of low-LET (photon) irradiation. However, there is an unmet need in space biology to investigate the consequences of chronic low-dose, high-LET radiation, which is particularly relevant in this context.

Gravitational forces during spaceflight

The difference in gravitational forces in space compared to earth, are another source for adverse health effects. The gravity that humans experience on Earth is about 9.81 m/s 2 , defined as 1 g (varies about 1% by location) 47 . However, space travelers are exposed to both reduced and increased gravity forces. In LEO, the forces amount to free fall, resulting in a gravity that is a millionth of that on Earth’s surface. In practice, perfect weightless conditions are impossible to attain due to disturbances from drag, vibrations, etc., and so the term microgravity (µg) is used to describe the actual conditions. The suppression of gravitational force, or its strong reduction, is responsible for the following effects: (1) decreased hydrostatic pressure, (2) no weight, (3) no sedimentation, and (4) no natural convection 48 . Those living on the Moon and Mars would experience about 1/6 and 1/3 the amount of gravity on Earth, respectively; while hypergravity of 3–7 times that on Earth can be seen during re-entry 49 . These gravitational alterations have an impact on blood flow, shear stress forces, cytoskeleton, cell adhesion properties, and mechanoreceptors 50 , 51 . Under microgravity, body fluid is displaced in the cephalad direction, causing ‘puffy face syndrome’ in astronauts. At the same time, the loss of loading in the lower extremities leads to decreased bone mass, muscle mass, and strength. Change in vascular dynamics under microgravity has been observed. Simulated microgravity in a rat model caused an increase in aorta stiffness 52 . In astronauts, femoral artery intima media thickness increased during 6 months of spaceflight 53 . Similar to the lower extremities, pelvic organs receive blood supply from the aorta and internal iliac arteries. Uterine blood flow is ~100 mL/min, whereas in a uterus in term pregnancy, this flow increases to 700 mL/min, which accounts for nearly 10% of the cardiac output 54 . Currently, we have limited knowledge of how gravitational forces affect pelvic and pituitary portal circulations. Also, we do not know if micro- or hypergravity impact utero-placental blood flow, which is crucial for healthy fetal growth. Therefore, it is important to understand the impact of gravitational forces on reproductive organs and their vascular dynamics. In the following sections, we will discuss gravitational studies focusing on reproductive tissues in more detail.

Reproductive endocrinology and developmental biology for Earth and beyond

To date, various models including mice, rats, salamanders, frogs, fish, and cockroaches have been studied to understand the effects of spaceflight on reproduction 53 . Some of these studies were conducted during actual spaceflights, while others were carried out under simulated microgravity (i.e., parabolic flights, hindlimb suspension and rotating wall vessels) 53 . In 2000, Jennings et al. reviewed the gynecological data and reproductive outcomes in U.S. female astronauts between 1991 and 1997 55 . The success rates for assisted reproductive technology (ART) in astronauts have been low, yet comparable to older patients undergoing ART 55 . Yet as of 2023, there has been no global update on the reproductive outcome data after space travels despite continued participation from female astronauts in space missions. There is a global need for a women’s health database that includes clinical, biochemical and omics information for spaceflight. Although literature exists on non-human species, there are still many unknown questions regarding the effects of the space environment beyond LEO on the human reproductive system.

As we navigate the intricate realms of reproductive endocrinology and developmental biology on Earth, this complex system has been marveled over since the beginning of time. Now, as we venture into space, new dimensions to our understanding have begun to unfold. In the next sections, we will review the normal physiology, alongside an exploration of the current space literature available. We will discuss ovarian steroidogenesis and the menstrual cycle elucidating the core processes of reproductive endocrinology. We will explore the circadian rhythm and associated hormonal regulations illuminating chronobiology. Finally, we will examine ovarian folliculogenesis and oocyte maturation while shedding light on ovarian dynamics and the aging process. It is important to note that even with successful oocyte development, the path to successful pregnancy hinges on the pivotal stages of fertilization, implantation, embryo development, and subsequent fetal growth to achieve a healthy live birth. During these complex steps, prenatal conditions shape the trajectory of health across a lifetime, forming the foundation of the Developmental Origins of Health and Disease (DOHaD) Hypothesis 56 .

The hypothalamic–pituitary–gonadal (HPG) axis, menstrual cycle, and ovarian steroidogenesis

The HPG axis is the primary regulator of menstrual cycle, ovarian steroidogenesis and folliculogenesis. Pulsatile hypothalamic secretion of gonadotropin-releasing hormone (GnRH) plays an essential role in releasing pituitary gonadotropins (FSH and LH), which, in turn, regulate gonadal function (Fig. 1 ). Frequency and amplitude of GnRH secretion change in follicular and luteal phases of the menstrual cycle. Thus, a physiologic menstrual cycle requires pulsatile GnRH secretion. Although there are limited data regarding the HPG axis during spaceflight, one study demonstrated lowered serum GnRH, FSH, LH, and testosterone levels in male rats exposed to simulated microgravity 57 . The fluid shift and its impact on the pituitary gland could be an explanation for the reported gonadotropin changes. Cephalad fluid shift due to microgravity has been observed during spaceflight and MRI studies showed increased pituitary deformation and change in cerebrospinal fluid dynamics during spaceflight 58 . Thus, these physiologic adaptations may impact the HPG axis.

The HPG axis controls the menstrual cycle via hormonal feedback loops during menstruation, follicular phase, ovulation, and luteal phase. Menstrual cycle irregularities have been reported in female flight attendants 59 , 60 . In 1978, the first bed rest study in females investigated gynecological data 61 . In this study, no significant change in the length of the menstrual cycle was noted after 17 days 61 . In rodent studies, data are conflicting regarding the effects of spaceflight on the estrous cycle in female mice during spaceflight 62 , 63 . A recent study reported possible estrous cycle activity 62 , whereas prior STS missions showed smaller ovaries, regression of corpora lutea, and cessation of estrous cycling 64 . Under simulated microgravity, female rodents showed less time in estrous phase 65 . On the other hand, hypergravity exposure extended the diestrus stage of the estrous cycle in rats 66 .There is limited data on human cycle variations as most female astronauts taking a form of hormonal contraception 61 . Hormone use has been associated with the risk of venous thromboembolism (VTE) in both pre- and postmenopausal women. Hormonal contraceptive use during spaceflight and the risk of VTE have been reviewed in another article 67 . It was revealed that women using combined oral contraceptives (COCs) during flight exhibit higher calculated blood viscosity than those not taking COCs 67 . Furthermore, due to the physiological changes during spaceflight, the pharmacokinetics of drugs may be different in space 68 . Currently, we have limited information on the pharmacokinetics of hormonal medications in the space environment. Knowing if the kinetics are different would change dosing and should be explored further.

Sex steroid hormones are essential part of the menstrual cycle. Ovarian steroidogenesis is the main source of sex steroid hormones (e.g., estradiol, progesterone) (Fig. 1 ). The two-cell two-gonadotropin theory is the main foundation of ovarian steroidogenesis and involves the interaction of theca and granulosa cells. In the ovary, steroidogenesis starts with cholesterol, the precursor of steroid hormones, and LH stimulates theca cells to produce androgens. Androgens then shuttle to granulosa cells and aromatize to estrogens via FSH-induced aromatase. Estrogens play a major role not only in the reproductive system, but also systemically promote bone health, cardiovascular health, immune function, and metabolism 69 . Estrogen deficiency is a known risk factor for decreased bone mineral density and osteoporosis. The bone mineral density is also negatively impacted by mechanical unloading, such as weightlessness experienced during spaceflight and bed rest studies, as well as exposure to radiation 70 , 71 . Therefore, both estrogen deficiency and spaceflight are independently associated with decreased bone mineral density, and their combined effects may have compounding impacts on bone health. Further, during the menopausal transition and menopause, women experience decreased estradiol levels and its systemic and metabolic consequences such as vasomotor symptoms, sleep disturbances, and changes in cholesterol profile. Currently, there is limited data on how estrogen receptors and signaling are affected by spaceflight in various organs 72 . Our previous study showed gene expression changes in estrogen-linked gene sets during spaceflight across various tissues in both rodent and human samples 72 . We still have limited knowledge on whether spaceflight has an impact on steroid hormone signaling pathways in reproductive tissues. One study showed that ovarian tissue estradiol concentrations of space-flown mice were not significantly different than their ground control counterparts 62 . Although ovarian expression of steroidogenic genes (i.e., Star , Cyp11a1 , Cyp17a1 , Cyp19a1 , and Hsd3b1 ) were not significantly different across groups, ovarian progesterone levels were lower in the flight group than the baseline cohort 62 . Simulated microgravity in mouse Sertoli cells results in the upregulation of Cyp19a1, which encodes aromatase 73 . Consequently, this leads to an increase in estradiol production 73 . Ovaries also produce testosterone and androstenedione, which are converted to estradiol and estrone via aromatization, respectively. Ovarian testosterone production is also stimulated by insulin and insulin-like growth factors (IGFs). Although insulin-linked gene expressions are altered during spaceflight in both human and rodent samples 74 , 75 , information is limited on how these genes and related pathways may change in reproductive organs. Ovarian steroidogenesis undergoes modifications throughout a woman’s life span. Thus, it is important to understand the stages of a woman’s life and the hormonal changes that occur during these stages, starting with puberty and continuing through her reproductive years, perimenopause and postmenopausal periods.

Endocrine effects of circadian rhythm alterations

Changes in the circadian rhythm may interfere with GnRH signaling and the HPG axis. The HPG axis is closely related to the circadian clock. Humans evolved to live in a 24-h light–dark cycle; however, the day cycle on the ISS is vastly different with the ISS orbiting the Earth every 90 min and will be different on other planets as well. Disruptions in sleep and circadian rhythm have an impact on fertility and pregnancy. Specifically, sleep dysregulation has been associated with menstrual irregularities 76 infertility, miscarriage, fetal growth restriction, preeclampsia, and preterm birth 77 , 78 . Therefore, it is critical to assess these effects.

In mammals, the circadian system is driven by the suprachiasmatic nucleus (SCN) located in the hypothalamus (Fig. 1 ). In female rodents, the SCN is necessary for generating the preovulatory surge via GnRH and LH secretion 79 . Both microgravity and hypergravity can alter circadian rhythm and clock genes 80 , 81 , 82 , the latter of which are expressed centrally, but also in reproductive organs where they are involved in the regulation of key steroidogenic genes, including Cyp19a1 and Hsd3b2 83 , 84 . Women who sleep less than 8 h display lower FSH levels, which may indicate functional impairments in GnRH pulsatility and resulting pituitary function due to altered circadian rhythm 85 . In addition, chronic insomnia increases pituitary adrenocorticotropic hormone (ACTH) and cortisol levels, associated with enhanced stress response which may disrupt HPG function 86 , 87 .

Ovarian clock gene expression has been associated with ovarian aging 88 . Ovarian clock genes were downregulated with aging and correlated with Anti-Müllerian hormone (AMH) levels 88 . Insulin is another hormone that is closely related to both circadian rhythm and HPG axis 89 . Insulin resistance has been linked to circadian rhythm changes 90 and was observed in both astronauts and rodents 74 , 75 , 91 . Sleep abnormalities such as short sleep duration, chronic insomnia and evening chronotype are all associated with insulin resistance 92 . Insulin signaling plays a role in ovarian physiology and is essential for lipid and glucose transport during ovarian folliculogenesis 93 and impaired insulin signaling is a major disruptor for female infertility 94 . Impaired insulin signaling not only affects nonpregnant women; overt insulin resistance during pregnancy can lead to gestational diabetes and associated neonatal risks including macrosomia, shoulder dystocia, hypoglycemia, and hyperbilirubinemia 95 . In summary, menstrual cycle dynamics are complex and involve ovarian steroidogenesis, recruitment of follicles and folliculogenesis, oocyte maturation during folliculogenesis, cyclic changes in the endometrium, which are coordinated by the HPG axis and feedback loops along with metabolic and cellular changes at the molecular level. This complex system is closely related to the circadian rhythm, involving both central and peripheral clock systems.

Furthermore, circadian rhythm alterations have been implicated in the incidence and biology of human cancers as well as DNA damage repair mechanisms, suggesting that circadian alterations could plausibly affect the rate of radiation-induced carcinogenesis 96 . Further research needs to highlight physiologic and pathophysiologic changes during spaceflight if they interfere with these intricate and interrelated steps.

Ovarian folliculogenesis, oocyte maturation, and aging

Women have a limited number of oocytes throughout their life span. Initially, a female fetus at 20 weeks of gestation possesses a maximum of 6–7 million oocytes. At birth, this number decreases to 1 to 2 million. The count steadily decreases as age advances, reaching around 1000 oocytes at 51 years old. Oocytes are supported by the follicles throughout folliculogenesis, a continuous process that involves follicle recruitment, selection, and eventual ovulation. Ovarian folliculogenesis and intraovarian signaling both play critical roles during oocyte maturation and quality. Hormones, calcium signaling, cytokines, growth factors, and the cytoskeleton are pivotal in this maturation process. Oocyte maturation progress is in synchrony with the ongoing folliculogenesis.

Ovarian folliculogenesis is a continuous process that has both gonadotropin-independent and gonadotropin-dependent phases, regulated by FSH, LH, and intraovarian factors such as AMH, activin, inhibin, growth differentiation factor-9 (GDF-9), bone morphogenic protein-15 (BMP-15), and gap junction proteins 97 . There is an interactive communication between the oocyte and follicle cells (i.e., granulosa cells). This complex system is understudied in the realm of human space biology. The effect of microgravity on rodent oocytes during follicle development has been studied using rotating wall vessels. In simulated microgravity, the arrangement of granulosa cells within follicles was disrupted as more than 50% of cells lost their polarity 98 . In a porcine model, simulated microgravity inhibited the proliferation of granulosa cells and arrested the cell cycle 99 . These changes would hinder cellular communication, thereby impacting folliculogenesis. In female mice, folliculogenesis is disrupted during spaceflight, with the majority of follicles in the flight group exhibiting atresia 64 . AMH is one of the regulatory hormones of folliculogenesis and is secreted by the granulosa cells of developing follicles. A dry immersion study on 12 women, designed to mimic microgravity conditions, revealed variations in serum AMH levels 100 . However, the median AMH levels remained relatively stable before and after immersion 100 . In contrast, inhibin B levels were higher, while LH and progesterone levels were lower post-immersion. Notably, subjects’ ages ranged from 22.7 to 40.8 years, which might have contributed to the observed variations. GDF-9 is another paracrine factor which regulates folliculogenesis. Microgravity exposure resulted in decreased number of follicles, and GDF-9 protein expressions along with adverse morphological effects on mice oocytes 101 . These morphological effects included disrupted mitochondria and Golgi, absent microvilli, and the appearance of multilamellar bodies and lipid droplets 101 . In another study, oocyte maturation rates were significantly lower under simulated microgravity (8.9% vs. 73% in μg vs. 1 g) along with disrupted meiotic spindle formation 102 . When exposed to microgravity, mice oocytes exhibited a decrease in the release of the first polar body, indicating further unfavorable effects of microgravity on oocyte maturation 98 . A recent study on human oocytes exposed to simulated microgravity demonstrated notable morphological changes in both mitochondria and smooth endoplasmic reticulum (SER) 103 . Under simulated microgravity, there was a decrease in the number of mitochondria and SER aggregates while mitochondria vesicle complexes increased. In addition, distinctive morphological disparities were observed such as elongated and dumbbell-shaped mitochondria, along with irregular borders and collapsed cristae. These morphological alterations may have implications for metabolism and fertilization. Although murine models are commonly used in reproductive biology research, it is important to highlight that there are physiological differences between mice and humans such as folliculogenesis takes longer in humans. Keep in mind that ovarian folliculogenesis is not a separate physiological process, as it synchronizes with sex steroid-induced changes in the endometrium (Fig. 2 ).

The endometrial, ovarian cycles are depicted in parallel with hormonal and gonadotropin fluctuations throughout the menstrual cycle.

An important point of distinction is that oocyte maturation and quality are related but different concepts. The oocyte maturation process involves structural and molecular changes including germinal vesicle breakdown, resumption of meiosis to metaphase, segregation of chromosomes, first polar body extrusion, and cytoplasmic maturation, which results in a haploid oocyte that is ready for fertilization. On the other hand, oocyte quality refers to viability and fertilization capacity of the oocyte, which is mainly assessed morphologically via evaluating distinct features such as ooplasmic granularity, perivitelline space, and zona pellucida 104 . Several factors can impact ovarian aging and quality, including age, genetics, and environmental factors (i.e., radiation, reproductive toxins) 105 .

As women age, oocyte quality declines and there is an increased risk of aneuploidy. In addition, telomeres at the end of chromosomes shorten with advancing maternal age. With each cell division, telomeres progressively shorten, and cell division stops when they reach a critical length, resulting in cellular senescence. Mitochondrial dysfunction and subsequent oxidative stress may contribute to telomere dysfunction 106 . The connection between aging and spaceflight has been explored in previous studies 107 . In the NASA twin study, telomere length increased during spaceflight and returned to its normal length upon return to Earth, suggesting that space travel might have an impact on the telomeres and telomerase activity 108 . Telomere dynamics was further studied in 11 astronauts who spent a year or less in the International Space Station 106 . Luxton et al. found that irrespective of the mission duration, there was an increase in the telomere length during spaceflight 106 . Upon returning to Earth, a decrease in telomere length was observed resulting in shorter telomeres than their preflight levels 106 . Additional findings were alterations in cell populations and significantly increased chromosomal inversion frequency during and after spaceflight 106 . Based on these findings, the authors proposed that in environments with chronic oxidative stress, a transient telomerase-independent adaptive response via activation of the Alternative Lengthening of Telomeres pathway may take place in somatic cells 106 .

In addition to parental DNA, the oocyte is also responsible for passing down cellular components and genetic materials to the offspring. While nuclear DNA is inherited from both parents, mitochondrial DNA, located in the cytoplasm, is inherited maternally from the oocyte’s cytoplasm. Considering that mitochondria is an organelle affected by the conditions during the spaceflight 2 , 101 , it is plausible to assume that spaceflight may also possess a risk to inherited mitochondrial DNA. The mitochondrial dysfunction that occurs in space has implications in instigating long-term health risks associated with the development of mitochondrial and metabolic diseases. Promising techniques involving the transfer of mitochondria, meiotic spindle, and ooplasm have emerged in reproductive endocrinology as potential solutions for specific forms of infertility and for preventing the inheritance of mitochondrial diseases.

The impacts of spaceflight, radiation, and microgravity on ovaries have been summarized in Table 3 . In summary, gamete maturation, epigenetics, and aging in space remains an understudied area. Furthermore, there have been reports of epigenetic changes during spaceflight in various organisms 109 , but our understanding of potential epigenetic effects on reproductive tissues, gametes, and subsequent embryos remains limited.

Fertilization and embryo development

Fertilization is the fusion of gametes (sperm and oocyte) to form a zygote. Following ovulation, fertilization usually occurs in the ampulla region of the fallopian tube. Successful fertilization requires more than sperm and oocyte interaction. A sperm must undergo physiological changes, a process known as capacitation, to fertilize the oocyte. Capacitated spermatozoa bind to the protective layer of the oocyte (zona pellucida), and after an acrosomal reaction, it penetrates through the oocyte. Once sperm enters the oocyte cytoplasm, maternal and paternal genetic fuses via pronuclear fusion followed by expulsion of the second polar body. Following fertilization, the zygote undergoes a series of cell divisions to proceed with embryo development. After successful cellular divisions, the formed blastocyst reaches the uterine cavity for implantation. The implanted embryo grows inside the uterine cavity. Ectopic pregnancy, seen in 2% of all pregnancies, is a condition in which the embryo implants and grows outside of the uterine cavity. When an ectopic pregnancy ruptures, it can be a life-threatening condition due to bleeding. The ciliary movement in the fallopian tubes aids the transfer of embryo toward the uterus; and it remains unknown if space travel is a risk factor or not for an extrauterine embryo implantation (i.e., ectopic pregnancy) due to altered cell adhesions and fluid dynamics resulting from microgravity.

Although microgravity’s effect on zygote migration to the uterus has not been studied, fertilization reactions in simulated microgravity and spaceflight have been investigated. Studies in the clinostat, a ground-based model to mimic microgravity, showed that the process of fertilization in vitro is not sensitive to the gravitational vector 110 . In the Micro-11 mission, human and bull sperms were sent to ISS to study capacitation and motility 111 , 112 . Critical motility parameters necessary for sperm capacitation and fertility, such as progressive motility, curvilinear velocity, and appearance of hyperactivated sperm were negatively compromised during spaceflight compared to ground controls 112 . Acrosome reaction rates were decreased in human and bovine sperm during spaceflight. Finally, significant sperm DNA damage was observed in flight as compared to ground controls 113 . The DNA fragmentation index (DFI%) was higher in spaceflight samples compared to ground controls at both 0 min and 60 minutes activation (0 min: FL = 19.3 ± 2.6% vs. GC = 8 ± 1.4%; 60 mins: FL = 32.7 ± 1.7% vs. GC = 12 ± 1.6%) 113 . In a recent study, mice were kept under microgravity (MG) conditions on the ISS for 35 days. The spermatozoa from artificial gravity (AG) and MG mice showed comparable fertilization rates in vitro to ground control (GC) males. Moreover, when the fertilized eggs were transferred to pseudopregnant females, there were no significant differences in the number of delivered pups among GC, AG, and MG spermatozoa. The growth rates and fecundity of the offspring were also similar across all groups 113 . This was followed up by another study which extended the duration of spaceflight 114 . Despite variations in the number of fertilized oocytes based on strain and duration of flight, most of the freeze-dried sperm demonstrated successful fertilization 114 . In another study, fertilization occurred under MG; however, embryo growth was impaired, and the birth rate was lower compared to 1 g controls 115 . Successful fertilization of gametes and transmission of genetic material to subsequent generations are crucial for the continuation of generations. To investigate epigenetic alterations in spaceflight and their transmission to future generations, Yoshida et al. evaluated the effects of 35 days of spaceflight on germ cells of male mice 116 .They observed changes in ATF7 activation, a transcription factor, in the testis as well as microRNA expression profiles in spermatozoa. Male offspring from these sperm samples demonstrated increased levels of DNA replication-related genes (i.e., Mcm genes) 116 . The potential reversibility of these spaceflight-induced stress-related epigenetic alterations remains to be explored. Further, space-flown sperm, used in the F1 progeny production, changed liver gene expressions in the next generation. In a separate study, long-term stay in space did not cause any DNA damage in freeze-dried sperm stored at the ISS for periods ranging from 9 months to 5 years and 10 months 117 . However, it is worth mentioning that inside the nucleus and cytoplasm, freeze-dried sperm lacks water molecules that are critical for free radical generation, and when compared to fresh sperm they entail higher resistance to radiation 117 . Another important aim of the study was to assess the fertilization potential of freeze-dried spermatozoa preserved in space. Although the fertilization failure rate was within the normal range, the average rate varied between different preservation periods in space 117 . The blastocyst quality was similar between those fertilized with spermatozoa obtained from ground control groups and those preserved in space and many of those resulted in birth of an offspring 117 . It is however important to emphasize here that some of the offspring from the latter group had a shorter life span despite having normal global gene expression profiles, normal reproductive potential, and producing second- and third-generation offspring without any abnormalities. Although some of these results are encouraging, transgenerational studies in space are limited and further studies are warranted.

A successful fertilization is not the only step toward pregnancy; proper embryo development required as well. The zygote undergoes multiple divisions (mitosis) to form an organized blastocyst during its transition from the fallopian tube to the uterus. Five to six days after fertilization, the embryo reaches the blastocyst stage, hatches out of its zona pellucida and begins the implantation process. Preimplantation embryo development in space has been studied in rodent models under both simulated gravity and during spaceflight. Fertilization of oocytes could be achieved under simulated microgravity (μg); however, morula and subsequent blastocyst formation (30% vs. 57%, μg vs. 1 g) and birth rates (5% vs. 21%, μg vs. 1 g) were significantly reduced compared to control groups 110 , 115 . A reduction in blastocyst rate (34.3% vs. 60.2%) was seen in actual spaceflight studies versus the GC group. The decreased blastocyst rate was associated with reduced blastocyst quality, a decreased number of cells, and increased DNA damage 118 , possibly attributable to microgravity’s known effects on cell cycle regulation and progression 119 , 120 . This assumption may further be supported by the observed induction of pSANK (stress-activated protein kinase) expression and cell cycle arrest in mouse embryos under simulated microgravity 121 . The mechanisms of disruption of cell cycle progression may include long noncoding RNA (lncRNA) expression changes that regulate pathways pertaining to protein transport, and cortical cytoskeleton functions that can affect migration of the pronucleus 122 . Furthermore, embryonic stem cells (ESCs) play a pivotal role during embryogenesis and organogenesis. They originate from the inner cell mass of the embryo, possess pluripotency, and differentiate into three primary germ layers: ectoderm, mesoderm, and endoderm. Each of these germ layers gives rise to specific tissues and organs. Research has indicated that exposure to microgravity changes the expression of genes involved in ESC differentiation and signaling pathways 123 . The cellular differentiation of trophectoderm and inner cell mass were also hindered in space-flown mice embryos 118 . The embryos from both space-flown and ground-irradiated mice not only showed decreased rates of blastocyst but also demonstrated changes in their DNA methylation profiles 118 . Space-flown mice embryos displayed a reduction in DNA methylation density. The low- and high-methylation Differentially Methylated Regions (DMR) were enriched in various biological processes, including histone modification, response to radiation, chromosome regulation, and embryo development 118 . Furthermore, when two-cell embryos were irradiated with Cs-137 gamma rays their DNA methylation levels decreased, correlating with increased doses of radiation. These effects were particularly robust after exposure to 2 mGy. In addition, when irradiated blastocysts were transferred to females, lower birth rates were observed in proportion to the radiation dose 118 . Based on current guidelines, the effects of radiation doses on human embryogenesis and organogenesis are also reviewed in Table 2 . These studies raise significant questions about the effects of spaceflight on the ability of normal embryo development but also on the epigenetic regulation of expressed DNA, as alluded to earlier. The impacts of spaceflight, radiation, and microgravity on mouse embryo development have been summarized in Table 4 .

In recent years, private companies and institutional researchers have been working towards understanding embryo development in the LEO to elucidate some of these questions. Embryo development is a dynamic process that involves changing the culture medium and monitoring developmental steps. Thawing and freezing of samples are often required during embryo research. On Earth, at IVF centers, embryos are vitrified and kept at −196 °C via liquid nitrogen, which is not available on the ISS. In 2022, Wakayama et al. developed a mouse embryo culture device, which allows astronauts to thaw and freeze samples without directly contacting the embryos using a high-osmolarity vitrification method to keep samples at −80 °C. Their method yielded a 90% embryo recovery rate and 80% of the samples reached blastocyst 124 . Future studies are needed to compare these results with human embryo samples donated for research.

Endometrium and endometrial receptivity

An euploid embryo with a high implantation potential and a receptive endometrium are prerequisites for pregnancy. Successful implantation requires embryo-endometrial synchrony, which is only possible during the “window of implantation” (WOI). In humans, this optimal window occurs 7–10 days after ovulation; in mice, it is 4 days post coitus. As aforementioned, upon fertilization of the oocyte, a zygote undergoes cellular divisions to form a blastocyst. Apposition of the blastocyst to endometrium starts the implantation process (Figs. 3 A, B and). Following adequate hormonal preparation of the endometrium, the main steps of implantation are apposition, adhesion, and invasion; all regulated by cytokines, growth factors, immune cells, cell adhesion molecules, and hormones (Fig. 3B ). Immune cells play essential roles not only during implantation but subsequently also in spiral artery remodeling, a process pivotal for placentation and pregnancy 125 . In this context, immune dysregulation observed during spaceflight 126 , and recent studies from the Inspiration 4 mission demonstrating sex-specific alterations in immune cells raise questions regarding successful implantation and endometrial receptivity 127 .

A Blastocyst development. This figure illustrates the stages of blastocyst development. B Blastocyst–endometrium crosstalk. This figure displays a preimplantation blastocyst and the signaling factors between the endometrium and blastocyst.

The endometrium is composed of dynamically changing proportions of different cell types, including glandular and luminal epithelium, stroma, endothelium, and bone marrow-derived immune cells 128 . A critical step in the establishment of pregnancy is stromal cell decidualization; a profound alteration in stromal cell structure and function that is dependent on the action of sex hormones, primarily progesterone. Decidualization regulates the maternal immune response for fetal allograft acceptance, promotes vascular remodeling to establish maternofetal communication and acts as a biosensor of embryo quality to prevent implantation of genetically abnormal embryos 125 . Using an in vitro decidualization model, simulated microgravity impaired decidualization, in part by impairing FOXO3a and AKT signaling 129 . Furthermore, in the mouse uterus, both alpha and beta estrogen receptors were downregulated during spaceflight compared to ground controls (Table 3 ) 64 . Similarly, lactoferrin is an estrogen-responsive protein in mouse uterine epithelial cells 130 and its mRNA expression levels decreased during spaceflight 64 . McMaster et al. showed that neutrophils, recruited by estradiol, were also a source of lactoferrin in the preimplantation mice uterus 130 .These findings further highlight the intricate interplay between the immune system and hormones, both of which may be impacted during spaceflight. Prior studies have shown systemic immune dysregulation during spaceflight 126 , but little is known about the effects of spaceflight on endometrial specific changes in immunity, and reproductive immunology.

Mechanoreceptors, whose signaling is modified under microgravity, are important for embryo implantation and dysfunctional mechanoreceptors may be involved in pregnancy complications, such as preeclampsia 131 , 132 . In summary, endometrium and reproductive immunology including maternal immune tolerance are understudied areas in space biology. Understanding the cyclic menstrual changes including proliferation and decidualization of the endometrium is also important in nonpregnant women as imbalance between estrogen and progesterone’s effect on endometrium can lead to abnormal uterine bleeding.

Pregnancy and developmental origins of health and disease hypothesis

Pregnancy is a complex process that involves physiological changes and adaptations in multiple organ systems to support the developing fetus. Cardiovascular, respiratory, genitourinary, gastrointestinal, endocrine, hematologic, and immune system changes are some of the examples that occur during this adaptation. Further, some conditions are also unique to pregnancy such as preeclampsia, gestational diabetes, and placental abnormalities. Thus far, to the best of our knowledge, there is no report of human conception during spaceflight. Various reproductive experiments on vertebrates and invertebrates such as cockroaches, fish, frogs, mice, and rats have been performed to understand how spaceflight affects fertilization and reproductive functions, with mixed results, which are summarized thoroughly in another review and rodent ones outlined below 133 . During the Cosmos mission in the 1980s, female and male rats were allowed to mate in space without monitoring 134 . Pregnancy resorption was demonstrated in 2 out of 5 female rats after landing 134 . Following this study, pregnant rats were flown to space to observe the effects of microgravity on parturition and litter size. One study reported prolonged labor in the flight group 135 , but others reported no significant changes in labor duration 136 . Variances in uterine contraction patterns were observed in space shuttle flights, such as increased lordosis 136 . Reduced progesterone secretion was detected in luteal cells isolated from the corpus luteum of pregnant rats 137 . In general, offspring from space-flown mice showed decreased birth weight 135 , 136 . In the 1990s, Medaka fish were the first reported vertebrate species to successfully mate in space during a 15-day mission 138 . The hatching rate and primordial germ cells formed in space were normal compared to controls 138 . Although these fish and invertebrate results are promising, humans have more complex biology and physiology. Therefore, uncertainty remains around the feasibility and safety of human conception, gestation, and labor in space. The impacts of spaceflight, radiation, and microgravity on rodent pregnancy have been summarized in Table 5 .

While the mechanisms underlying labor are only partially understood, some of the known molecular components have been studied in spaceflight. Connexins are gap junction proteins responsible for allowing coordinated contractions of the myometrium during labor and their expression increases at term. Connexin 43 is a critical gap junction protein expressed in the human and rat uterus and regulated by sex steroids 139 , 140 , 141 . One study demonstrated reduced myometrial connexin 43 during spaceflight, raising a potential concern about its effects on labor 142 . Another important component of uterine contraction is the secretion and action of oxytocin. Oxytocin is synthesized in the hypothalamus and released into the bloodstream by axons projecting from the hypothalamus to the posterior pituitary. Oxytocin plays a key role during labor, postpartum, and lactation. It causes uterine contractions in labor and is used as a medication to augment both labor and prevent postpartum hemorrhage. Gravitational and circadian rhythm changes may alter oxytocin synthesis and/or release. During a 14-day mission, rats flown to space showed a 27% reduction in pituitary oxytocin and vasopressin levels 143 . In another study, prepubertal female rats were flown to space for 16 days and then 18 weeks after landing, vasopressin levels returned to normal, but oxytocin levels were still reduced compared to the control group 144 . Oxytocin is also decreased when rats are exposed to hypergravity 145 . Oxytocin has extrauterine roles beyond its uterine functions, including potential effects on bone building and mood 146 . Oxytocin is also known as a social bonding hormone. Social isolation and prolonged living in a confined environment are features of spaceflight that may alter vasopressin, oxytocin, and serotonin receptor binding in a sex-dependent manner 147 . Not only the effects of microgravity but also hypergravity were examined using centrifugation methods to mimic the launch and re-entry phases. Exposure of pregnant rats to hypergravity showed unfavorable effects in terms of decrease in pregnancy rates and increased neonatal mortality 148 . On earth, pregnancy is considered a contraindication for extreme environments, like those with high pressure and temperatures, such as scuba diving. In terms of human data, a review published in 2000 outlined pregnancy after spaceflight 55 . The mean maternal age at the time of delivery for women who have been in space was 40. The mean age of the six women who had spontaneous miscarriage after spaceflight was 41. The advanced maternal age observed in the female astronaut cohort could be the result of career prioritization rather than a direct effect of spaceflight. This data also represents the cohort from shuttle missions, which had shorter durations compared to current missions.

Environmental factors, toxins, and pollutants are important factors to consider for reproductive health, pregnancy, and prenatal development. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that environmental factors during early development of life can have a profound and long-lasting impact on an individual’s health as well as susceptibility to diseases later in life. Exposure to environmental stressors and adverse nutritional conditions before or during pregnancy was shown to result in intergenerational and transgenerational epigenetic inheritance; a non-DNA sequence-based inheritance of a modified phenotype across generations 149 . This type of inheritance occurs through alterations in the pattern of gene expression by mechanisms such as DNA methylation, histone modification, and small RNA transmission 149 . Supporting this notion, a study conducted by Pembrey et al. demonstrated an anecdote of a paternal grandfather’s food supply was associated with mortality risk ratios of grandsons but not granddaughters, demonstrating a transgenerational but also sex-specific response 150 . Moreover, a series of studies utilizing rats as subjects demonstrated that susceptibility to diabetes and obesity was increased when rats were undernourished in utero for 50 generations, whereas nutrient recuperation for the subsequent two generations was not sufficient to reverse the resulting metabolic profile and epigenetic alterations, nor to mitigate the risks of developing obesity and diabetes 151 . Thus, optimization of nutrition and maternal weight is crucial during pregnancy, including prioritizing a balanced diet and appropriate vitamin intake to support fetal development. Prepregnancy counseling and screening is important to prevent certain comorbidities 152 . For instance, folic acid supplementation should be encouraged to prevent neural tube defects, and checking for iron and vitamin D deficiencies to provide appropriate supplementation is recommended. Dietary needs and caloric intake recommendations of pregnant and lactating women differ significantly from those of nonpregnant women and also vary per trimester and postpartum 153 . It is also important to note that 30 min of daily exercise is recommended, which could be a unique challenge in anti-gravity conditions. There are other routine recommended screenings throughout pregnancy such as ultrasound for fetal anatomy, gestational diabetes, sexually transmitted disease, and Rh status screening. All these above factors could present unique challenges, especially considering limited availability to bring medical and laboratory equipment, as well as limited nutritional resources in the space environment compared to Earth.

In summary, both direct and indirect space-related factors could affect the ability to conceive and pregnancy at various stages. It is important to consider and further investigate the influence of these factors before embarking on the idea of pregnancy in space.

Unintended pregnancy

Most female astronauts opt to use contraceptive methods 154 . Even with perfect adherence to contraceptive methods, the risk of pregnancy is not eliminated 155 . For instance, unplanned pregnancy rates in the first year of oral contraceptives is 9% with typical use, whereas it is 0.3% with perfect use 155 . One of the main causes of oral contraceptive failure is adherence. In addition, oral contraceptives are metabolized by the liver via the cytochrome p450 system. Certain antiseizure medications and antibiotics such as carbamazepine, phenytoin, and rifampin induce the p450 system which may increase oral contraception metabolism and decrease their efficacy. Prolonged diarrhea and vomiting are other conditions that may interfere with the absorption of contraceptive pills. Space adaptation syndrome (space sickness) is a subtype of motion sickness that presents with nausea and vomiting. It can be seen in 60–80% of space travelers in the first days of gravitational changes 156 . A space traveler who is on oral contraceptive pills and experiencing severe space sickness syndrome needs to be aware of possible absorption interference. There is also a risk of oral contraception failure after bariatric surgery, thus a space traveler with a history of bariatric surgery should be aware of effective contraceptive methods.

Another consideration is the risk of thrombosis, which differs depending on the type of contraceptive. The risk of thromboembolism is increased in combined oral contraceptive users as 3–9 in 10,000 women 157 . The Virchow’s triad is the main foundation underlying thrombus formation: vascular/endothelial injury, stasis, and hypercoagulability. Incidental occlusive internal jugular vein thrombosis was diagnosed in one of the ISS crew members during a mission 158 . Thus, before prescribing oral contraceptives, it is important to have a discussion with space travelers about their specific underlying risk factors and potential aggravating factors such as prolonged immobility or inherited thrombophilia. An alternative to contraceptive pills is the use of long-lasting progestin-only contraceptives, which can be used highly effectively in averting unwanted pregnancies from months to 8 years, and safe in women in whom estrogen-containing formulations are contraindicated. Thus, contraceptive methods should be individualized as their advantages and contraindications may vary.

Even with the more invasive contraceptive methods such as vasectomy and tubal sterilization, there is a slight possibility of unintended pregnancy. Failure rate (post-procedure pregnancy rate) depends on the method of tubal occlusion chosen. For instance, women who underwent postpartum salpingectomy have pregnancy rates of 6.3 and 7.5 per 1000 procedures at 5 years and 10 years, respectively 159 . On the other hand, for males who underwent vasectomy, the pregnancy rate is 11.3 per 1000 procedures at 5 years 159 . It is worth noting that some methods are not immediately effective and may require use of an additional method. For example, most men become azoospermic 3 to 6 months after the vasectomy procedure. While the number of commercial spaceflights and the emergence of space tourism is on the rise, we remain uncertain about the safety and feasibility of human conception in the space environment. Additionally, even if a successful and safe conception occurs, pregnancy outcomes in space remain uncharted territory. Therefore, as mentioned earlier, to prevent unintended pregnancies, space travelers should consult their obstetrician-gynecologist providers regarding contraception options, preflight pregnancy tests and precautions against unintended conception should also be addressed during these consultations.

Looking to the future of space biology

Cutting-edge research in gravitational biology and biomedical engineering is centered on experimental cell studies and explores tissue engineering in a space environment, including the 3D organoids. Organoids can be used for understanding tissue structure and function, hormonal regulations, early developmental biology research, disease models, and drug testing 160 . A few examples include mice bioprosthetic ovaries created by 3D-printed microporous hydrogel scaffolds 161 and a microfluidic platform supported ovary for hormone production 162 .

Advancements in technology also had an impact on surgical techniques. Currently, robotic-assisted surgery is commonly performed with a surgeon controlling the robotic arms from a console. The use of robotic-assisted surgery in space has been reviewed in another article 163 . Communication delay and its impact on team performance is an important concept for remote tasks and telesurgery. For example, at the greatest distance, ~24 min of communication latency is expected between Earth and Mars 163 . In the future, during space travel, with the advent of smart surgery glasses that can transmit intraoperative content 164 and improvements in haptic feedback 165 telesurgery may be utilized for the management of gynecologic emergencies such as ovarian torsion, cyst rupture or for a ruptured ectopic pregnancy.

Another development in the field of medical robotics is swimmable micro-robots or nanobots 166 . These are robotic devices designed to navigate and perform tasks inside the human body and they have the potential to enable remote-controlled minimal invasive procedures as well as targeted drug delivery. Although they are still in the research phase, they show great promise for the future of diagnosing and treating medical conditions.

While significant scientific achievements are occurring worldwide, it is also important to establish ground-based tools and methods for replicating microgravity. Thus far, traditionally hindlimb suspension and rotating wall vessels have been utilized to mimic microgravity 167 . Magnetic levitation approach by utilizing anti-Helmholtz configuration of magnets via diamagnetophoresis has been proposed and validated to simulate the microgravity conditions 168 . This approach allows reduction (if not full elimination) of one continuous force field (i.e., gravitation field) by another continuous force field (i.e., magnetic field). The biocompatible environment mimicking the weightlessness condition was achieved by utilizing gadolinium (Gd) solutions (i.e., FDA-approved MRI contrast agent), shown to be nontoxic, iso-osmolar to human blood cells 169 . The same platform enables levitated cells within capillary to be exposed to a low-intensity laser beam via microscope. For instance, an earlier study showed that, at the UV-irradiated area of levitated RBCs, lymphocytes, and PMNs, cells raised their equilibration heights. Instantly after UV stimulation was shut down, cells returned to their starting heights, while RBCs equilibrated at a lower height than its starting height, possibly suggesting that intracellular, UV-induced ROS raised the magnetic susceptibility of RBCs 169 . These studies can be expanded to monitor several cellular activities affecting female reproductive health in the presence of microgravity and/or irradiation and have implications for longer missions to Mars and advanced precision medicine 170 . Novel spatiotemporal monitoring of human cells, followed by nucleic acid and protein analyses, will pave the way for studies in distinctive signaling mechanisms that appear only during microgravity settings.

The relationship between spaceflight and reproduction is an emerging area of research that is necessary as an increasing number of humans venture into space. Hormones necessary for reproduction also play an important role in other organ systems. Sex differences involving tissue response to space-associated risk factors and multi-organ analysis are also crucial areas to be investigated during spaceflight. With so little data on spaceflight and its effect on endocrine signaling, ovulation, reproduction, cryopreservation of gametes and/or embryos or other fertilization preservation actions will be important to astronaut well-being.

Some of the obvious limitations on reproductive space research include inconsistent duration of spaceflights, different age and strain of animals, lack of data in menstruating species (e.g., humans, apes, and Old-World monkeys) and human models. We also do not have information on how space travel will affect women with gynecological issues such as diminished ovarian reserve, polycystic ovarian syndrome (PCOS), endometriosis, and uterine fibroids. Moreover, as we are slowly transitioning from governmental led crewed activities in low Earth orbit by highly selected and trained career astronauts to more commercially led missions by the general public, future studies are needed to explore the unanswered aspects of mammalian reproduction in space so that results can be interpreted, and information can be used to achieve safe space travel and colonization.

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Acknowledgements

BM is supported by the Department of Obstetrics and Gynecology at the University of South Florida. N.S. acknowledges the support of the Osteopathic Heritage Foundation through funding for the Osteopathic Heritage Foundation Ralph S. Licklider, D.O., Research Endowment in the Heritage College of Osteopathic Medicine. We would like to thank our medical illustrator, Ezgi Bozogullarindan, for Figs. 1 , 2 , 3 A. Figure 3B was created with BioRender.com.

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P.A. is no longer affiliated with Department of Dermatology and Allergy, University Hospital, LMU, Munich, Germany

Authors and Affiliations

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, Tampa, FL, USA

Begum Mathyk & Anthony N. Imudia

Shady Grove Fertility San Diego, San Diego, CA, USA

Alexander M. Quaas

Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, CT, USA

Cihan Halicigil & Murat Basar

Blue Marble Space Institute for Science, Exobiology Branch, NASA Ames Research Center, Moffett Field, CA, USA

Fathi Karouia

Space Research Within Reach, San Francisco, CA, USA

Center for Space Medicine, Baylor College of Medicine, Houston, TX, USA

BioServe Space Technologies, Smead Aerospace Engineering Science Department, University of Colorado Boulder, Boulder, CO, USA

Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA

Nicolas G. Nelson

Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, Tampa, FL, USA

Ozlem Guzeloglu-Kayisli, Miriah Denbo & Umit A. Kayisli

Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA

Lauren M. Sanders, Ryan T. Scott & Sylvain V. Costes

Blue Marble Space Institute of Science, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA

Lauren M. Sanders & Afshin Beheshti

KBR, Moffett Field, CA, USA

Ryan T. Scott

Molecular and Cellular Biology, School of Biosciences, University of Sheffield, Sheffield, UK

Ana Paula Guevara-Cerdán

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Sunnyvale, CA, USA

Michael Strug & Brent Monseur

Ohio Musculoskeletal and Neurological Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA

Nathaniel Szewczyk

Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA

Christopher E. Mason

The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA

World Quant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University, Durham, NC, USA

Steven L. Young

School of Mechanical Engineering, Koç University, Istanbul, Türkiye

Savas Tasoglu

Koç University Translational Medicine Research Center (KUTTAM), Koç University, Istanbul, Türkiye

Boğaziçi Institute of Biomedical Engineering, Boğaziçi University, Istanbul, Türkiye

Physical Intelligence Department, Max Planck Institute for Intelligent Systems, Stuttgart, Germany

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

Afshin Beheshti

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Mathyk, B., Imudia, A.N., Quaas, A.M. et al. Understanding how space travel affects the female reproductive system to the Moon and beyond. npj Womens Health 2 , 20 (2024). https://doi.org/10.1038/s44294-024-00009-z

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Frontiers for Young Minds

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Meet BioSentinel: The First Biological Experiment In Deep Space

Recently, NASA launched a rocket called Artemis-I toward the Moon! The mission objective was to test the safety of the Space Launch System for future human travel into deep space. But vehicle safety is not the only concern for space travelers. Space radiation is an invisible danger to astronauts because it can damage the body’s cells and potentially lead to serious health problems. How do we study the effects of space radiation on cells? Meet BioSentinel! BioSentinel is a small satellite deployed from Artemis-I that carries yeast cells and a sensor to measure space radiation. The job of BioSentinel is to transmit data from the cells in deep space back to Earth. In this article, we will explore the BioSentinel mission, discuss how the data are obtained and transmitted, and give examples of how the data from BioSentinel will help scientists better understand the effects of space radiation on living things.

Did you know that scientists are sending living organisms into space, to study how space radiation affects life forms [ 1 ]? It is true! Recently, the National Aeronautics and Space Administration (NASA) deployed a small satellite , called BioSentinel, from the Artemis-I rocket. BioSentinel carried yeast cells into space, to help scientists learn more about the effects of space radiation. This article will explore the BioSentinel mission and why it is important for space travel.

What is the BioSentinel Mission?

The Artemis-I rocket ( Figure 1A ) started its journey to the Moon on November 16, 2022. The aim of the mission was to test the safety of the Space Launch System for future human journeys into deep space. Vehicle safety, however, is not the only risk for space travelers. Astronauts are exposed to radiation while they are in space, which can lead to serious health effects. Therefore, alongside the primary launch objectives of Artemis-I, small satellites were also deployed to test other risks of space travel, with BioSentinel being one of them. The BioSentinel satellite consists of a shoe box-sized unit ( Figures 1B , C ) that holds yeast cells and the necessary electronics and solar panels to power the satellite in space.

Figure 1 - (A) The Artemis-I rocket was sent to space with the main mission of testing the safety of the Space Launch System.

Figure 1 - (A) The Artemis-I rocket was sent to space with the main mission of testing the safety of the Space Launch System.
(B) Artemis-I also deployed BioSentinel, a shoe box-sized satellite. (C) BioSentinel was loaded with yeast cells, to study the effects of space radiation on living things in deep space. BioSentinel also has solar panels for power and contains the electronics necessary to send information back to Earth (Image Credit: adapted from NASA.gov ).

Why Study Space Radiation?

Space radiation consists of solar particles originating from the Sun and galactic cosmic rays originating outside our solar system. (For more information on space radiation, see this Frontiers for Young Minds article .) Space radiation includes high-energy particles that travel through space at very high speeds and can pass through things like spacecrafts and the spacesuits of astronauts [ 2 ]. Space radiation can harm humans and other living things if they are exposed to it for too long, because it can damage DNA and other important cell parts. (To learn more about space flight health risks see this Frontiers for Young Minds article .) DNA damage can lead to serious health problems like cancer. Most of the time, cells fix damage correctly; but in some cases, damage is too complex for the cell to repair. In these cases, the cell might die or repair itself incorrectly, leading to mutations in its DNA. Cells with mutations can start multiplying uncontrollably, and that is how cancer forms over time. Many of the health problems caused by space radiation, like cancer, are delayed effects—so astronauts would not get sick until later in their lifetimes, after they have returned to Earth. By studying space radiation, scientists hope to learn more about how it affects living things and how to protect astronauts.

How Does BioSentinel Study Space Radiation?

BioSentinel uses yeast cells ( Figure 2D ) to study how living things respond to space radiation [ 3 ]. Yeast cells are single-celled organisms commonly used to help bread dough rise or in the fermentation process used to make beer. The type of yeast used in BioSentinel is frequently used in research in many types of labs around the world. It was the first organism to have its DNA fully sequenced, for example. Yeast cells are important in scientific experiments because they share many similarities with human cells, and therefore the results obtained from yeast cells can give us clues about human health. Yeast cells can withstand the rigors of space travel, especially since they can be dried out and only activated by liquid when they are needed. Yeast cells can also be modified to make them either more sensitive or more resistant to space radiation, to better understand how human cells might respond to space missions.

Figure 2 - (A) BioSentinel contains a radiation sensor, to measure space radiation, and microfluidic cards containing yeast cells, to monitor the effects of space radiation on living cells.

Figure 2 - (A) BioSentinel contains a radiation sensor, to measure space radiation, and microfluidic cards containing yeast cells, to monitor the effects of space radiation on living cells.
(B, C) The microfluidic system is made up of multiple smaller card units, and it can deliver nutrient-containing fluids to the yeast cells to help them survive. The microfluidic system also delivers the dye used for measuring DNA damage in response to space radiation. (D) Yeast cells (Image Credit: Adapted from NASA.gov ).

In BioSentinel, the yeast cells are placed in special containers called microfluidic cards , where the cells receive the nutrients needed to stay alive ( Figures 2B , C ). As discussed earlier, space radiation can damage DNA. Damage to yeast DNA can change their metabolic activity , meaning how they change nutrients into energy. A special dye is delivered to the microfluidic cards, which changes color based on the metabolic activity of the yeast cells [ 1 , 3 ]. Monitoring the change in metabolic activity allows scientists to see how space radiation affects the yeast cells ( Figure 3 ). Additionally, there is a radiation sensor inside BioSentinel that measures the space radiation ( Figure 2A ). Data from the microfluidic cards and the radiation sensor are sent back to Earth, where scientists can analyze those data to see how radiation causes DNA damage and how the yeast cells respond.

Figure 3 - (A) To monitor the response of yeast cells to radiation during the BioSentinel mission, a special blue dye is added to the microfluidic cards.

Figure 3 - (A) To monitor the response of yeast cells to radiation during the BioSentinel mission, a special blue dye is added to the microfluidic cards.
(B) When yeast cells are healthy and metabolically active (using nutrients to survive and grow), the dye changes from blue to pink. (B) However, if radiation damages yeast DNA, the rate of metabolic activity can change. The cells with damage remain blue longer, while the cells not affected by radiation turn pink faster.

What Happens After the BioSentinel Mission?

The Artemis-I spacecraft has safely returned to Earth, but BioSentinel will remain in space collecting data. The mission is set for 6 months, during which data from the radiation sensor and microfluidic cards are periodically transmitted to Earth. After the mission is complete, scientists will analyze all the data to learn more about how space radiation affects living things. Furthermore, the data will be compared to experiments on Earth and on the International Space Station, and also compared with computer simulations of the radiation-containing space environment. These data, together with information from other space studies, could be used to develop new ways to protect astronauts from radiation during long space missions—to the Moon, Mars, and beyond! Data could also have important implications for cancer research and other areas of human health related to space travel.

The BioSentinel mission is an exciting project that aims to study the effects of space radiation on living organisms. By sending yeast cells into deep space, scientists hope to learn more about how radiation affects cells and how to protect astronauts on long-duration space missions, as NASA prepares astronauts to return to the Moon and eventually travel to Mars and beyond. The results of the BioSentinel mission could have important implications for human health, and we cannot wait to see what scientists learn from this groundbreaking mission.

Radiation : ↑ Transmission of energy through waves or traveling fast particles.

Satellite : ↑ An object that goes around (orbits) a planet.

Solar Particles : ↑ Energetic particles released from the Sun into space.

Galactic Cosmic Rays : ↑ High energy particles of different types originating from outside of our solar system that travel through space at very fast speeds.

DNA : ↑ A molecule found in the nucleus of living organisms that contains genetic information (genes) telling living organisms how to look and function.

Mutation : ↑ Changes in the DNA of organisms that can make the cells function differently.

Microfluidic Card : ↑ Container in the BioSentinel that provides fluid and nutrients to keep the yeast cells alive.

Metabolic Activity : ↑ The chemical reactions in cells that help to convert nutrients into energy for survival.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

This work was supported by the NASA Langley Research Center Cooperative Agreement 80LARC17C0004 and by the Human Research Program under the Space Operations Mission Directorate (SOMP) at NASA. The BioSentinel program at the NASA Ames Research Center (ARC) was supported in part by the NASA Advanced Exploration Systems (AES) Division/Exploration Systems Development Mission Directorate (ESDMD). The authors would like to acknowledge Dr. Kathleen Miller for her help with creating the figures and general guidance.

[1] ↑ Ricco, A. J., Santa Maria, S. R., Hanel, R. P. and Bhattacharya, S. 2020. BioSentinel: a 6U Nanosatellite for Deep-Space Biological Science. IEEE Aerosp. Electron. Syst. Mag . 35:6–18. doi: 10.1109/MAES.2019.2953760

[2] ↑ Simonsen, L. C., Slaba, T. C., Guida P., Rusek A. 2020. NASA’s first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research. PLoS Biol. 18:e3000669. doi: 10.1371/journal.pbio.3000669

[3] ↑ Santa Maria, S. R., Marina, D. B., Massaro Tieze, S., Liddell, L. C., Bhattacharya, S. 2020. BioSentinel: long-term saccharomyces cerevisiae preservation for a deep space biosensor mission. Astrobiology 20:1–14. doi: 10.1089/ast.2019.2073

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Parasites: Ones That Bite, Infect, and Live in GI Tract

Limiting Exposure

There are various types and subtypes of parasites. The three main classes of parasites are protozoa, helminths, and ectoparasites, which can cause disease.

If you contract a parasite, you may live with it for years without noticing any symptoms develop. When symptoms do occur, they can typically affect the gastrointestinal tract and lead to symptoms such as nausea and vomiting, diarrhea, or stomach pain.

This article discusses the various types of parasites that live in humans, their symptoms, and how to tell if you have one.

Joos Mind / Getty Images

Parasites That Live in Humans

Parasites are tiny organisms that live on a host. They sustain life by getting food from the host, sometimes at the expense of the host’s health. Out of all the parasites that exist, only three main classes can cause disease in humans. They are ectoparasites, helminths, and protozoa.

Ectoparasites

Ectoparasites burrow into the skin or attach themselves to their host and stay put for an extended period of time. In some cases, these parasites can live on the body for weeks or months. These types tend to live off a person’s blood while they are attached.

These parasites can lead to human disease by acting as vectors of infectious pathogens. For example, Lyme disease is a bacterial infection passed to humans through a bite from an infected tick. The pathogen doesn’t harm the tick, but it will harm the host.

Parasite Examples: Ectoparasites

Several types of ectoparasites can cause human disease, including:

Helminths are larger multicellular organisms that you can see with the naked eye when they are in the adult stages. Not all helminths act parasitic, as some can survive without a host, making them free-living. When a helminth has reached adulthood, it can produce larva and eggs.

Helminths often take the shape of a worm and typically live in the gastrointestinal (GI) tract, causing issues. In some cases, these parasites can also enter the blood, lymphatic system , or tissue under the skin.

Parasite Examples: Helminths

Various types of helminths can lead to disease in human hosts, such as:

Thorny-headed worms

Protozoa are one-celled microorganisms that, like helminths, can require a host to live but can also be free-living. Once they have infiltrated a human body, they can multiply, causing them to grow in numbers and drive the onset of serious infections.

Typically, people get protozoa through the fecal-oral transmission route after eating or drinking something contaminated by fecal matter containing protozoa. They are often found in the intestines but can also live in the blood or tissue of humans if they are contracted via an arthropod, such as a mosquito feeding on a person’s blood.

Parasite Examples: Protozoa

Protozoa that can cause human disease include:

Sarcodina (amoeba, Entamoeba )
Mastigophora (flagellates, Giardia and Leishmania )
Ciliophora (ciliates, Balantidium )
Sporozoa ( Plasmodium, Cryptosporidium )

Symptoms Parasites Cause

The symptoms a person develops after contracting a parasite will differ, depending on the type.

Ectoparasite symptoms can include:

A rash in the area where they burrowed into the skin
Red, wavy, or raised lines on the skin
Small red and raised bumps
Scratch marks

Helminths typically fail to cause symptoms in human hosts. If they do, the symptoms can include:

Abdominal pain
Loss of blood and protein
Rectal prolapse (rectum bulges out of the anus)
Slowed physical and cognitive growth in children

Protozoa often affect the gastrointestinal tract and can lead to symptoms such as:

Loss of appetite
Urticaria (hives)
Weight loss

Parasites and the Onset of Bowel Disorders

A protozoa infection is often associated with the onset of irritable bowel syndrome because of the way it affects the gastrointestinal tract.

Testing for Parasites

If you believe you have a parasitic infection, seeing a healthcare provider is essential. They'll be able to help you with where to go for the proper testing. Typically, tests are done at specific testing centers or labs nationwide.

Various tests will be conducted, including:

A fecal stool exam (a sample of your own feces is taken to the lab), known as an ova and parasite test
Endoscopy or colonoscopy , which uses a small tube with a camera on the end to get a look inside the gastrointestinal tract to look for parasites or evidence of a parasitic infection
Blood tests to detect parasitic infections that can be detected in the blood
X-ray and other imaging tests, including magnetic resonance imaging (MRI) or computed tomography (CT) scans to look for lesions within the body caused by a parasite
Scotch tape test, which involves placing tape against the anal opening a few times and then looking for parasitic eggs under a microscope

Once the results are ready, a healthcare provider will review them with you to determine the next steps regarding treatment.

Risks of Untreated Symptoms From Parasites

Parasitic infections can be severe if they are left untreated. Over time, the parasites continue to damage the host.

If they are left untreated for a more extended period, people can start to experience serious health consequences, including:

Congenital disabilities, preterm labor, and low birth weight can all occur if the parasite is contracted while pregnant
An increased risk of contracting other infectious diseases, including human immunodeficiency virus (HIV)
Heart failure

Who Is Most at Risk for Untreated Parasitic Infections?

Untreated parasitic infections are becoming more common in the United States. According to data, those living in impoverished communities are the most at risk of contracting and developing an untreated parasitic infection.

Treating Parasites

Treatments are recommended for most parasites. However, ectoparasites could be as easy as removing the organism from your skin, washing yourself and your clothes and bedding, and cleaning the home from any infestation that may cause the parasites to burrow into you again.

For other types of parasites, medical treatment is needed and often entails using antiparasitic drugs. They can include:

Artemisinin derivatives
Quinine-related compounds
Niclosamide
Albendazole derivatives
Nitazoxanide
Pyrimethamine

These medications are designed to kill parasites within the body while helping you excrete them from your system. When taking the drugs, you will be given a set schedule, dosage, and treatment duration that must be adhered to ensure that the parasites are dead and gone from your body.

Some alternative and complementary therapies that may be suggested to you alongside a primary treatment can help speed up the process of getting rid of a parasite. Some options include:

Changing your diet to avoid simple carbohydrates
Eating more raw foods, such as garlic, pumpkin seeds, pomegranates, beets, and carrots, all of which can be used to kill parasites
Eating more fiber
Consuming probiotics to keep the digestive tract healthy
Using digestive enzymes to restore health to the digestive tract to make it a poor environment for parasites to thrive in
Using supplements, such as vitamin C or zinc, for symptom relief

Severe Parasitic Infection Treatment

If parasites cause a severe infection, other therapies may have to be explored to help rid the body of the infestation. These include surgery and more potent drugs.

How to Limit Parasite Exposure

To reduce your risk of contracting a parasite, you can:

Wash your hands frequently, especially after touching animals or animal feces.
Follow proper food-handling techniques to avoid contaminated food .
Be careful of your contact with animals that may have parasitic infections.
Avoid sharing needles with others.
Avoid eating uncooked animal products, such as fish and crab , as well as raw aquatic plants.
Always wash produce before consuming.
Always treat outdoor water before drinking.

How Contagious Are Parasites?

Parasites are contagious and are typically spread in the following ways:

Fecal-oral transmission
The consumption of contaminated food or water
Close person-to-person contact

During International Travel

If you are traveling to a location where the risk of contracting a parasite is higher, there are some things you will want to do to ensure you don’t accidentally get a parasitic infection. They include:

Use only packaged water (for drinking, brushing your teeth, washing your face, etc.).
Avoid drinking beverages with ice as the water used to make the ice may be contaminated.
Avoid precooked, homemade meals.
Get vaccinated .
Get tested for parasites upon returning from an exotic location.

Although parasitic infections are not as common as other types, such as viral or bacterial, they can still be prevalent in the United States. The three main parasites that cause human disease are transmitted in similar ways, with the exception of ectoparasites.

If you contract a parasite, you will likely need some form of treatment to rid it from the body to avoid long-term complications, such as seizures, heart failure, and, in a worst-case scenario, death. The best way to prevent parasitic infections is to protect yourself by practicing good hygiene, avoiding potentially contaminated food and water, and following proper food-handling methods.

Gizaw Z, Engdaw GT, Nigusie A, Gebrehiwot M, Destaw B. Human ectoparasites are highly prevalent in the rural communities of northwest ethiopia: A community-based cross-sectional study . Environ Health Insights. 2021 Jul 21;15:11786302211034463. doi:10.1177/11786302211034463

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By Angelica Bottaro Bottaro has a Bachelor of Science in Psychology and an Advanced Diploma in Journalism. She is based in Canada.

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About this story

Human Health during Space Travel: State-of-the-Art Review

Nitin Kumar Singh

Richard A. Scheuring

Emmanuel Urquieta

Eric M. Bershad

Timothy R. Macaulay

Scott Kaplin

Stephen F. Kry

Thais Russomano

Marc Shepanek

Raymond P. Stowe

Andrew W. Kirkpatrick

Timothy J. Broderick

Jean D. Sibonga

Andrew G. Lee

Brian E. Crucian

Associated Data

1. Introduction

1.1. Medical Screening and Certification Prior to Space Travel

1.2. Effects on the Cardiovascular System

1.3. Effects on the Gastrointestinal System

1.4. Effects on the Immune System

1.5. Effects on the Hematologic System

1.6. Oncologic Effects

1.7. Effects on the Neurologic System

1.7.1. Effects on the Neuro-Ocular System

1.7.2. Effects on the Neuro-Behavioral System

1.8. Effects on the Musculoskeletal System

1.9. Effects on the Pulmonary System

1.10. Effects on the Dermatologic System

1.11. Diagnostic Imaging Modalities in Space

1.12. Medical and Surgical Procedures in Space

1.13. Lifestyle Management in Space

1.14. Future Directions for Precision Space Health with AI

2. Conclusions

Acknowledgments

Abbreviations

Funding Statement

Conflicts of Interest

Health Research Is Needed Now before Sending Civilians to Space

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Keeping astronauts healthy in space isn’t easy − new training programs will prepare students to perform medicine while thousands of miles away from Earth

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