Effects of spaceflight aboard the International Space Station on mouse estrous cycle and ovarian gene expression

Abstract

Ovarian steroids dramatically impact normal homeostatic and metabolic processes of most tissues within the body, including muscle, bone, neural, immune, cardiovascular, and reproductive systems. Determining the effects of spaceflight on the ovary and estrous cycle is, therefore, critical to our understanding of all spaceflight experiments using female mice. Adult female mice (n = 10) were exposed to and sacrificed on-orbit after 37 days of spaceflight in microgravity. Contemporary control (preflight baseline, vivarium, and habitat; n = 10/group) groups were maintained at the Kennedy Space Center, prior to sacrifice and similar tissue collection at the NASA Ames Research Center. Ovarian tissues were collected and processed for RNA and steroid analyses at initial carcass thaw. Vaginal wall tissue collected from twice frozen/thawed carcasses was fixed for estrous cycle stage determinations. The proportion of animals in each phase of the estrous cycle (i.e., proestrus, estrus, metestrus, and diestrus) did not appreciably differ between baseline, vivarium, and flight mice, while habitat control mice exhibited greater numbers in diestrus. Ovarian tissue steroid concentrations indicated no differences in estradiol across groups, while progesterone levels were lower (p < 0.05) in habitat and flight compared to baseline females. Genes involved in ovarian steroidogenic function were not differentially expressed across groups. As ovarian estrogen can dramatically impact multiple non-reproductive tissues, these data support vaginal wall estrous cycle classification of all female mice flown in space. Additionally, since females exposed to long-term spaceflight were observed at different estrous cycle stages, this indicates females are likely undergoing ovarian cyclicity and may yet be fertile.

Spaceflight alters insulin and estrogen signaling pathways

“…A few published studies show insulin resistance parameters may change during space ight but data is con icting, suggesting either decreased insulin or no change 19 , 20 . Similarly, data on estrogen signaling are con icting with one study revealing downregulation of ESR1 and ESR2 in the uterus 21 whereas a recent study found no alterations in estrogen receptor expression in rodent ovaries 22 . To address these gaps in our knowledge of insulin and estrogen signaling in response to space ight we examined these signaling pathways across multiple tissues in rodents from the same mission as well as in a group of astronauts and a set of commercial space ight participants/astronauts.…”

“…Samples were collected and processed as previously described 22 , 54 . Mouse carcasses were removed from − 80°C storage and thawed at room temperature for 15-20 minutes.…”

Extraterrestrial Gynecology: Could Spaceflight Increase the Risk of Developing Cancer in Female Astronauts? An Updated Review

“…Studies of female mice that were maintained on the International Space Station (ISS) for 37 days prior to euthanasia in space (eliminating re-entry stressors) revealed evidence that these female mice could be detected at different stages of the estrous cycle post-mortem, suggesting that some females were likely exhibiting estrous cyclicity [37]. Mouse embryos flown on China's SJ-10 biosatellite completed a series of cell divisions leading to blastocoel morphology during spaceflight, but both the rate of blastocyst formation and blastocyst quality were impaired [38].…”

The oestrous cycle and skeletal muscle atrophy: Investigations in rodent models of muscle loss

“…Studies have begun to assess alterations to oestrous cyclicity in association with muscle disuse and atrophy. A recent study in spaceflown mice in low earth orbit concluded that spaceflight itself does not appear to affect oestrous cyclicity (Hong et al, 2021); however, this conclusion was based on a single measurement of vaginal wall staining, which does not describe alterations to the oestrous cycle itself.…”