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Progress on mammalian reproduction in microgravity

AI generated image of an expectant mother with her developing fetus in Earth orbit after mammalian reproduction has been validated via higher animal models through all stages of pregnancy for a safe level of gravity. An appropriate level of radiation shielding would also be required and is not shown in this illustration. Credits:DALL∙E 3

We are one step closer to determining the gravity prescription for human reproduction in space. Okay, so we still don’t have the green light for having children at destinations in space with less than normal Earth gravity or higher radiation environments….yet. But a team of Japanese scientists report positive results after running an experiment aboard the International Space Station in 2019 that examined mouse embryos cultured in both microgravity and artificial gravity in space, then compared them to controls on Earth after a few days of development. The researchers published their results in a paper in iScience.

The researchers developed equipment and a protocol for freezing two-cell embryos after fertilization on the ground and launching them to the ISS where they were thawed then split into two groups, one allocated to growth in microgravity, the other treated with spin gravity to artificially simulate 1g. A control group remained on Earth. The procedure was designed to be executed by untrained astronauts. Cultured growth continued for 4 days after which the samples were preserved and refridgerated until they could be returned to Earth for analysis.

The samples were also monitored for radiation with a dosimeter and as expected aboard the ISS, were exposed to radiation levels higher then developing fetuses experience on the ground but far lower than those known to exist in deep space outside the Earth’s atmosphere and protective magnetic field. Still, this can be a “worst case” data point for radiation exposure to developing embryos as it is unlikely that pregnancy would be ethically sanctioned at higher levels.

Upon thawing by astronauts, the embryos were cultured through initial mitosis to eventual cell differentiation and blastocyst formation. A blastocyst is the multicellular structure of early embryonic development consisting of an an outer layer of cells called the trophectoderm surrounding a fluid-filled cavity in which an inner cell mass (ICM) called the embryoblast eventually develops into the embryo.

The study was concerned with how gravity may influence cell differentiation, the placement of the ICM within the blastocyst and if radiation effects gene expression in the these cells which will later develop into the fetus. Gene expression within the trophectoderm is also critical for proper development of the placenta.

The results were very promising as the data showed that there were no significant effects on early cell differentiation during embryo development and that proper gene expression manifested in microgravity when compared to 1g artificial and normal Earth gravity.

A human blastocyst with the inner cell mass at upper right. Credits: Wikipedia

A highlight of the paper implied that the results indicate that “Mammals can thrive in space.” It is too early to make such a bold statement with only this one study. It should be noted that this experiment only focuses on one early stage of embryo development. Conception in microgravity is not addressed and as pointed out by Alex Layendecker of the Astrosexological Research Institute, may have a whole other set of problems that raise ethical concerns as may the effects of lower gravity on later stages of gestation, in actual live birth and in early child development.

No matter how positive these recent results appear to be for early embryo development, as was determined by a landmark experiment on pregnant mice during the Shuttle era, we already have a data point on mammalian fetal development in later stages of gestation in microgravity: serious brain developmental issues were discovered in mice offspring born after exposure to these conditions. So mammalian reproduction in microgravity may start out relatively normally (assuming conception is successful) but appears to have problems in later stages, at least according to the limited data we have so far. On the bright side, the recent study found that 1g artificial gravity had no significant effects on embryo development.

Clearly more data is needed to determine which level of gravity will be sufficient for all stages of mammalian reproduction in space. Fortunately, SpaceBorn United is working on this very problem. They have plans for research into all stages of human reproduction in space to enable independent human settlements off Earth. SpaceBorn CEO Egbert Edelbroek in a recent appearance on The Space Show described upcoming missions later this decade that will study mammalian conception and embryo development using the company’s assisted reproductive technology in space (ARTIS). They have developed a space-embryo-incubator that will contain male and female mouse gametes, which upon launch into orbit, will initiate conception to create embryos for development in variable gravity levels. After 5-6 days the embryos would be cryogenically frozen for return to Earth where they would be inspected and if acceptable, placed in a natural womb for the rest of pregnancy and subsequent birth. If successful with mice the the company plans experiments with human stem cell embryos and eventually human gametes.

The gravity prescription for human reproduction in less than normal Earth gravity is still not known. But at least researchers are starting to gather data on this critical factor for long term biologically sustainable space settlement.

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Moon-Mars dumbbell variable gravity research facility in LEO

Conceptual illustration depicting the deployment sequence of a LEO Moon-Mars dumbbell partial gravity facility serviced by SpaceX’s Starship. Left: Starship payloads being moored by a robot arm. Center: 1.6 m ID inflatable airbeams (yellow) play out from spin access and mate with dumbbell end modules. Rectangular solar arrays deploy by hanging at either end as spin is initiated via thrusters at Mars module. Right: Full deployment with Starship and Dragon docked at spin axis hub. Credits: Joe Carroll via The Space Review

There may be no single human factor more important to understand on the road to long term space settlement than determination of the gravity prescription (GRx) for healthy living in less than Earth normal gravity. What do we mean by the GRx? With over 60 years of human space flight experience we still only have two data points for stays longer than a few days to study the effects of gravity on human physiology: microgravity aboard the ISS and data here on the ground. Based on medical research to date, we know that significant problems arise in human health after months of exposure to microgravity. To name a few, osteoporosis, immune system degradation, diminished muscle mass, vision problems due to changes in interocular pressure and cognitive impairment resulting memory loss and lack concentration. Some of these problems can be mitigated with a few hours of daily exercise. But recovery upon return to normal gravity takes considerable time and we don’t know if some of these problems will become irreversible after longer term stays. We have virtually no data on human health at gravity levels of the Moon and Mars, as shown in this graph by Joe Carrol:

Graph of the correlation between human health vs gravity showing the two data points where we have useful data. Whether the relationship is a linear function or something more complex is an unknown of great importance for space settlement. Credits: Joe Carrol presentation at Starship Congress 2019 and Jon Goff post on Selenium Boondocks Nov 29, 2005

The more important question for permanent space settlements is can humans have babies in lower gravity? If we go by the National Space Societies’ definition, an outpost will never really become a permanent space settlement until it is “biologically self-sustaining”. We evolved over millions of years at the bottom Earth’s gravity well. How will amniotic fluid, changes in cell growth, fetal development and human embryos be affected during gestation under lower gravity conditions on the Moon or Mars? There are already indications that problems will arise during mammalian gestation, at least in microgravity as experienced aboard the ISS.

To answer these questions, Joe Carroll suggests the establishment of a crewed artificial gravity research facility in LEO which he described last month in an article in The Space Review. He proposes a Moon-Mars dumbbell with nodes spinning at different rates to simulate gravity on both the Moon and Mars, which covers most of the planetary bodies in the solar system where settlements would be established if not in free space. The facility could be launched and tended by SpaceX’s Starship once the spacecraft is flight worthy in the next few years in parallel with Elon Musk’s plans to establish an outpost on Mars. Musk may even want to fund this facility to inform his long term plans for communities on Mars. If his goal is for the humanity to become a multiplanetary species, surely will want to know if his settlers can have children.

Carroll’s design connects the Moon and Mars modules with radial structures called “airbeams” which will allow crew to access the variable gravity nodes in a shirtsleeve environment. The inflatable members are composed of polymer fiber fabric which can be easily folded for storage in the Starship payload bay. Crews would be initially launched aboard Dragon until the Starship is human rated.

“Eventually, rotating free-space settlements will get massive enough to use other shapes, but dumbbells plus airbeams seem like the key to useful early ones.”

The paper addresses details on key operating concepts, docking procedures, emergency protocols, and the implications for long term settlement in the solar system.

There may even be a market for orbital tourism to experience lower gravity that could make funding for the facility attractive to space venture capitalists, especially if it is located in an equatorial orbit shielded from ionizing radiation by the Earth’s magnetic fields. As the technology matures, older tourists may even want to retire in orbital communities that offer the advantage of lower gravity as their bodies become frail in their golden years.

Humankind’s expansion out into the solar system depends on where we can survive and thrive in a healthy environment. If ethical clinical studies on lower mammals in a Moon/Mars dumbbell clears the way for a healthy life in lunar gravity then we can expand out to the six largest moons including our own plus Mars. If the data shows we need at least Mars gravity, then the Red Planet or even Mercury could be potential sites for permanent settlement. But if nothing below Earth normal gravity is tolerable, especially for mammalian gestation, it may be necessary to build ever larger rotating O’Neillian free space settlements to expand civilization across the solar system. There are vast resources and virtually unlimited energy if we need to do that. But it will take considerable time and careful planning to establish the vast infrastructure needed to build these settlements. If human physiology is constrained by Earth’s gravity then space settlers will want to know this information soon so that the planning process can be integrated into space development activities about to unfold on the Moon and beyond. If Musk finds out that Mars inhabitants cannot have children and wants to establish permanent communities beyond Earth, would he change course and switch to O’Neillian free space settlements?

“If we do need sustained gravity at levels higher than that of Mars, it seems easier to develop sustainable rotating settlements than to terraform any near-1g planet.”

Listen to Joe Carroll answer my questions about his Moon/Mars dumbbell facility from earlier this month on this archived episode of The Space Show.

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Reproduction off Earth and its implications for space settlement

Launch of the Space Shuttle Atlantis (STS-66) on November 3, 1994. The mission carried an experiment called NIH.Rodent 1, the first of only two study’s to date on rats launched at mid-pregnancy and landed close to full term to study the effects of microgravity on reproduction. Credits: NASA

In a MDPI Journal Life paper, Alexandra Proshchina and a team* of Russian researchers summarize the research that has been performed thus far on reproduction of invertebrates in space. As mentioned in the article, the only data we have on mammalian reproduction in microgravity since the dawn of the space age is from two experiments carried out over 26 years ago. The studies looked at pregnant rats launched aboard the Space Shuttle on missions STS-66 and STS-70 in 1994 and 1995 respectively, and there have never been any births of mammals in space. This huge knowledge gap on reproduction in space is problematic for human space settlement. Yet Elon Musk, The Mars Society, and other groups are charging ahead with plans for cities on Mars. What if we discover that humans cannot have healthy babies in 0.38g? SSP has covered the quest for determining the gravity prescription before looking at JAXA’s effort to at least start experimenting with artificial gravity in space, albeit on adult mammals (mice). We are still waiting for JAXA’s published results of 1/6g experiments carried out in 2019.

The data from the Space Shuttle program only looked at part of the gestation period (after 9 days) and only in microgravity. The results did not bode well for reproduction in space. Some findings “…clearly indicate that microgravity, and possibly other nonspecific effects of spaceflight, can alter the normal development of the brain itself.”

Histological cross section through a representative rat brain from NIH.Rodent 1 experiment from STS-66. Left side (a) is low magnification and right side (b-d) are high magnification. Red arrows show areas of neurodegeneration. 1 – Nasal cavity, 2 – olfactory nerve, 3 – olfactory bulb, 4 – eye, 5 – cortex telencephali, 6 – hippocampus, 7 – fourth ventricle, 8 – cerebellum. Credits: Alexandra Proshchina et al.*

So we have this one piece of data for reproduction in microgravity and nothing in higher gravitational fields except what we know here on Earth in 1g.

Would partial gravity like on the Moon or Mars be sufficient for normal fetal development in rats (or mammals in general, especially humans) during the full gestation period? If problems are identified could it be extrapolated to human reproduction? The fact that homo sapiens and their ancestors evolved on Earth in 1g for hundreds of thousands of years is a big red flag for future space colonists that hope to settle on the surface of planetary bodies and have children.

We don’t know how lower gravity conditions could affect embryonic cell growth. How would the changes in surface tension and embryo cell adhesion be altered in these environments? We have very little data on cellular mechanisms and embryonic alterations that lower gravity may induce that could affect fetal development.

“There are also many other questions to be answered about vertebrate development under space flight conditions.”

A recent report on giving birth in space by SpaceTech Analytics looks at many of the factors that need to be considered for human reproduction off Earth. Most problems could be potentially mitigated through engineering solutions such as radiation protection, medical innovations tailored for space use, life support technology, etc. In this entire presentation the authors gave very little consideration to partial gravity affects on human embryos and child birth. One slide (number 70) out of 85 discusses these issues.

It is clear that more and longer term experiments will be necessary to determine how partial gravity affects the reproduction and development of mammals before humans settle space. Some researchers are actually considering genetic modification to allow healthy reproduction in space, and the ethical considerations associated with this course of action. Obviously, such a drastic methods would come only if there was no other alternative. One would think that building O’Neill type habitats rotating to produce 1g of artificial gravity would be preferable to such extreme measures.

Clearly, we need a space based artificial gravity laboratory to carry out ethical clinical studies on the gravity prescription for human reproduction, starting with rodents and other lower organisms. SSP recently covered a kilometer long version of such a facility that could be deployed in a single Falcon Heavy launch. And don’t forget Joe Carroll’s proposal for a LEO partial gravity test facility. Doesn’t it make sense to invest in such a facility and do the proper research before (or at least in parallel to) detailed engineering studies of colonies on the Moon or Mars intended for long term settlement? This research could inform decision making on where we will eventually establish permanent space settlements: on the surface of smaller worlds or in free space settlements envisioned by Gerard K. O’Neill. Elon Musk may want to consider such a facility before he gets too far down the road to establishing cities on Mars.

* Authors of Reproduction and the Early Development of Vertebrates in Space: Problems, Results, Opportunities: Alexandra Proshchina, Victoria Gulimova, Anastasia Kharlamova, Yuliya Krivova, Nadezhda Besova, Rustam Berdiev and Sergey Saveliev.