Prolonged Spaceflight Linked to Female Reproductive Dysfunction and Transgenerational Effects in Landmark Mouse Study
核心洞察
A 42-day spaceflight on the ISS led to reduced fertility in female mice, with fewer pups born compared to ground controls.
Offspring of space-flown dams showed altered body weights, behavioral changes, and reduced fecundity over a nine-month period.
Transgenerational effects were observed in grandpups, including altered responses to a high-fat diet, suggesting heritable changes.
Female mice exposed to a 42-day spaceflight aboard the International Space Station (ISS) experienced measurable reproductive dysfunction, and their offspring and grand-offspring exhibited persistent physiological and behavioral changes, according to a new study published in the Proceedings of the National Academy of Sciences (PNAS). The research, led by Lane Christenson, Ph.D., professor in the Department of Cell Biology and Physiology at the University of Kansas Medical Center, represents the first-ever examination of long-term space exposure on female reproductive physiology conducted in mice.
The study, part of the NASA Rodent Research 20 mission, launched in November 2023 aboard a SpaceX rocket. It examined the impact of prolonged spaceflight on the female reproductive axis, including ovulatory capacity, implantation rate, and fecundity, as well as behavioral, metabolic, and functional outcomes in F1 and F2 offspring.
Fertility Effects in Space-Flown Females
Following their return to Earth, the female mice that spent 42 days in space were mated with males. The researchers found that these flight females had slightly fewer pups compared with the control group of ground-based females that never went to space. The findings point to a direct effect of the space environment on the female reproductive system.
Altered Outcomes in First-Generation Offspring
The pups born to space-flown dams drew immediate attention from the research team. "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 male and female pups also demonstrated changes in behavior and muscle contractility. "That was very interesting and suggested that spaceflight had an impact on the dam, her oocytes, and possibly the conditions within the uterus where the pups grew," Christenson added.
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. This finding suggests that offspring from flight dams were born with a reduced number of eggs in their ovaries.
Transgenerational Inheritance in Grandpups
Christenson extended the experiment to examine the grandpups of the flight dams. The researchers found some of the same physiological changes in the grandpups that were observed in the original pups, including reduced egg counts. Additionally, Matt Morris, Ph.D., also in the Department of Cell Biology and Physiology at KU Medical Center, investigated whether the grandpups of space-flown mice would respond to a metabolic challenge—a high-fat diet—similarly to grandpups of control mice. Both male and female grandpups in the flight lineage responded differently than the control grandpups, indicating that some changes induced by spaceflight can be inherited across generations.
"That's a pretty unique finding for spaceflight research," said Christenson.
Potential Mechanisms and Next Steps
The next phase of this research aims to uncover the molecular and cellular mechanisms underlying these changes. It is already known that space travel can cause some organs in the body to age prematurely, Christenson noted, and it stands to reason that the ovaries and the eggs within them could also be affected. "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."
Implications for Human Space Exploration
As NASA pursues plans for a lunar base near the moon's South Pole and longer-range ambitions to send humans to Mars, and with increased interest in space tourism, understanding the long-term effects of spaceflight on human health is a critical consideration. "It is absolutely important that astronauts and tourists know the long-term effects of spaceflight before they go," Christenson said. He emphasized that as more younger people venture into space, they will want to understand the effects on their organ systems, including the reproductive system. "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."
The study was supported by NASA Space Biology grant #NNX15AB48G/#80NSSC24M0072, with additional funding from the NIH COBRE P20GM144269, the University of Kansas Diabetes Institute, the Kansas Space Grant Consortium, NSERC, and the Canadian Space Agency.