Can humans reproduce in space? Mouse breakthrough on ISS a promising sign
(Click on images to enlarge.)
If you think this article is about how humans can have sex in zero gravity, you will be disappointed. Humans are mentioned, but the topic revolves around studies on how well embryos from mammals will be able to deal with environmental issues in space. Those issues mainly include weightlessness and exposure to gamma rays. Since the heading mentions mice, be prepared for background material science has accumulated on that and other creatures, too. It all relates to the eventual goal of humans living and reproducing outside Earth as we make more steps toward colonizing the Moon and Mars.
Interest in long-term living on the Moon or Mars is gaining ground. The Artemis program is aimed at setting up lunar base camps, and NASA has even set up a one-year CHAPEA habitat on Earth to simulate living on Mars. Astronauts have already spent months living on the International Space Station (ISS), with lots of physiological data collected on their exposure to isolation, microgravity, and radiation. But the safety of developing fetuses in space is part of the long list of unanswered questions on people's minds.
In the early days of spaceflight, tests were being run on animal physiology to see what negative effects there might be when life met zero gravity and exposure to radiation. Beginning in 1948, dogs, monkeys, chimpanzees, birds, mice, rates, rabbits, turtles, wine flies, mealworms, turtles, insects, spiders, jellyfish, newts, frogs and frog eggs, fish, fungi, and bacteria were sent up for various types of tests. Some were performance tests (like how a spider would weave a web in zero gravity), but others were sent to test how they survived radiation, too. For example, NASA's Biocore Experiment sent five pocket mice along with the Apollo 17 astronauts and compared extensive biological examinations with mice on Earth.
Upon their return, they were examined thoroughly for many factors that might relate to damage caused by radiation, but virtually none were found. Because of the size of spacecraft (and the International Space Station), it's been difficult to test large numbers of animals in space. The limited time of some experiments are due to using an orbiter or Space Shuttle, too, and that has an effect on what sort of exposure is being measured. For example:
- 1967. Kosmos 110. Two dogs in space for 22 days
- 1985. Space Lab 3 experiments aboard Space Shuttle. Six rats for 12 days
- 1987. Kosmos 1887. Ten rats in orbit for 12 days
- 1989. Cosmos/Kosmos 2044 joint Russian-international mission. Ten male rats, 14 days in space
- 1988, 1989. TEXUS sound rocket flight, 7 minutes. Frog eggs were fertilized in space
- 1992-1994. Space Shuttle. Frog embryos developed to blastula and gastrula stages, 1 week
- 2009. Mice Drawer System aboard Space Station. Six mice spent 91 days on the ISS
- 2019. International Space Station. Twelve male mice were raised aboard the ISS for 35 days
The statistics alone on such small numbers of animals make it difficult to assess accurately what changes may have occurred. And the animals in space did not breed there, nor did any mammal have birth in space.
Japanese researchers at the Advanced Biotechnology Center, University of Yamanashi decided to send frozen mouse embryos to the ISS for a few days in 2021 to see what would happen as they developed. The goal was to observe any changes and try to relate them to the effects of microgravity.
Below, you can see part of the normal development process. After sperm and egg unite to create a one-celled zygote, it divides rapidly. At the 16-cell stage, there are basically two types of cells: the inner ones called the ICM (inner cell mass), and the outer layer. After one more cell division, the outer cells secrete fluid inward to create the liquid-filled cavity. This combination of cavity, inner, and outer cells is called a blastocyst (which means "sprout sac").
This process take place as the embryo travels to the uterus, as shown below. You can see that the blastocyst is upside down ready to implant into the wall of the uterus.
So, now we have a group of cells in a lopsided configuration. Is its formation (or its fate thereafter) affected by zero gravity (or microgravity)?
What each cell in 2-cell, 4-cell, 8-cell, 16-cell, or 32-cell groupings does and where they end up in a blastocyst is not known. That can be important because the outer layer forms the placenta, and the ICM contributes to the formation of the fetus. The lopsided grouping of ICM cells inside the blastocyst made some scientists wonder if they grew together because gravity forced their them to. Also, when the blastocyst reaches the uterus, it must stick to it and be implanted to avoid it being washed out. The part of the blastocyst that makes contact is the outer membrane outside the ICM. Does attachment require gravity to make sure it touches properly, or is it just a biochemical difference in the outer membrane cells?
Mouse pregnancies are only 21 days long, and the time needed to reach the blastocyst stage is about 4 days after the zygote is formed (as you can see from the earlier diagram). Microgravity conditions have not been shown to adversely affect reproduction in sea urchins, fish, amphibians, and birds. But mammalian embryos develop a bit differently, and since humans are mammals, the Japanese experiment is a valid one. The Japanese sent up 2-celled embryos in frozen storage, and thawed them out in orbit.
Two-celled embryos were thawed and cultures in the same way on Earth, and differences were compared. They even grew embryos on the space station in regular microgravity conditions and under an artificially induced 1-g (normal Earth) gravity by rotating them in a special incubator to see whether something other than gravity off Earth would potentially have any effect. After 4 days, the blastocysts were preserved in a formaldehyde solution before returning to Earth.
One result was clear: embryos grown in space produced about the same number of cells in the blastocysts as the embryos did on Earth with normal gravity. In the graph below, you can see the Earth control blastocysts compared to the two groups in space (one with artificial 1-g gravity, one with microgravity). The TE means the cells on the outside of the blastocyst. The photo shows the ones they harvested in space.
There were some noticeable differences:
- on Earth, 60% of the 2-cell embryos developed into blastocysts, but in space 29.5% did for the artificial gravity test and 23.6% did at zero gravity.
- the rate of DNA damage and gene expressions of blastocysts were no different in all three environments (this takes into effect gravity as well as radiation)
- in three of the 12 blastocysts from the zero-gravity test, the ICM cells bunched together in two places, instead of the usual one place
Rats and mice sent into space earlier bred but didn't produce any offspring for unknown reasons. Because the space-bound embryos were preserved in formaldehyde, they couldn't be implanted into mice after they returned to Earth, so that step in this project was incomplete. But the Japanese researchers have two alternate plans.
“We are planning to conduct an experiment on the ISS to create the same environment as the uterus to see if a blastocyst can be implanted there, and will observe the following development.”
“I would also like to conduct an experiment in which astronauts freeze blastocysts that have been cultured for four days on the ISS, bring them back to the ground, thaw them and implant them in female mice to see if they produce offspring.”
In an earlier experiment, the same researchers sent up frozen mouse sperm cells, which were stored on the ISS for 288 days. After they were returned to Earth, they were examined and used to fertilize mice. Some damage to the sperm's DNA was found, but the baby mice that grew did not appear any different from controls, and the rate of fertilization was also no different. The researchers felt that normal DNA-repair mechanisms in the mouse egg might have helped restore them to normal.
The Japanese researchers have been studying mouse development for many years. This latest work simulated Earth gravity aboard the ISS, but earlier work simulated microgravity on Earth using unique 3D rotational devices called clinostats.
All of the data is being compared, and Professor Wakayama of this research team put it best in 2009:
“We are planning to perform similar experiments at different gravities, such as Moon gravity (1/6G) or Mars gravity (1/3G),” he says. “I want to know how much gravity is necessary to perform normal reproduction.”
