Could prolonged space travel impact the female reproductive system and subsequent generations?

When the Artemis II astronauts conducted a 10-day flyby of the moon in April, it was the first crewed lunar mission in more than 50 years. It also helped set the stage for NASA’s planned lunar base, a place for astronauts to live and work near the moon’s South Pole, and for longer-range ambitions to send humans to Mars.

With plans like these in the works and the increased interest in space tourism, human health in space is a critical consideration. “It is absolutely important that astronauts and tourists know the long-term effects of spaceflight before they go,” said Lane Christenson, Ph.D., professor in the Department of Cell Biology and Physiology at the University of Kansas Medical Center, who specializes in reproductive health research.

From decades of research, it’s already known that space travel is hard on the body. The lack of gravity in space affects the cardiovascular system, bone density and muscle mass, and radiation exposure in space puts people at higher risk for cancer and heart disease. Now, new animal-based research published in the Proceedings of the National Academy of Sciences and led by Christenson has taken us one step closer to understanding the potential effects of prolonged space travel on female fertility and reproductive health. The study, which was conducted in female mice, also examined the effects on their offspring (pups) and the offspring of the offspring (grandpups).

Christenson’s study — the first-ever examination of long-term space exposure on female reproductive physiology conducted in mice — was launched into space in November 2023 aboard a SpaceX rocket bound for the International Space Station. In collaboration with scientists at NASA’s Ames Research Center, the research focused on mouse fertility and changes in offspring behavior, growth and physiology.

The female mice, after spending 42 days in space, were mated with males following their return to Earth. The researchers found that females that went to space had slightly fewer pups compared with the control group (female mice that never went to space). Additionally, the researchers examined the pups to see if the mothers’ prior space exposure affected them. What they saw in the offspring sparked interest.

“We noticed immediately that the weights of the pups that were born to the mice that were flown in space were greater, especially the females,” said Christenson. Both the male and female pups also had changes in behavior and muscle contractility. “That was very interesting and suggested that spaceflight had an impact on the dam (mother), her oocytes (eggs) and possibly the conditions within the uterus where the pups grew.”

Moreover, when female offspring born to the flight dams were allowed to mate, these females had significantly fewer pups over a nine-month period — both fewer litters and fewer pups in each litter — than the female offspring from control dams, suggesting these offspring from flight dams were born with fewer number of eggs in their ovaries.

Christenson then decided to extend the experiment and look at the grandpups of the flight dams. And they found some of the same physiological changes in the grandpups that were found in the original pups, including fewer eggs.

Additionally, Matt Morris, Ph.D., also in the Department of Cell Biology and Physiology at KU Medical Center, asked whether the grandpups of space-flown mice would respond to a metabolic challenge — a high-fat diet — similarly to the grandpups of control mice. Both male and female grandpups in the flight lineage responded differently than the control grandpups. This means that not only did the flight affect the mice in space and their pups directly, but some of these changes also can be inherited across generations. “That’s a pretty unique finding for spaceflight research,” said Christenson.

The next step for this research is to learn how, on a molecular and cellular level, space flight causes these changes and how that may translate to humans. It is already known that space travel can cause some organs in the body to age prematurely, Christenson said. So it stands to reason that the ovaries, and eggs in them, could also be affected. How would that happen? “We think it involves changes in the mitochondria and possible epigenetic modifications — changes to the proteins around the DNA that affect gene expression,” he said. “These are the follow-up studies that we need to do, with the samples we already have collected.”

As more people venture into space, more younger people are likely to go, Christenson noted. “They are going to want to know the effects of long-term space travel on their organ systems including the reproductive system,” he said. “And we need to know the effects of space flight, so these astronauts and tourists can better prepare for flight, and so that new ways to protect and potentially mitigate these effects can be devised.”