Impact of simulated galactic cosmic radiation exposure on ovarian follicle development in mice

Exposure to galactic cosmic radiation (GCR) during deep space missions poses substantial risks to female reproductive (ovarian) and overall health, presenting a fundamental challenge for future exploration missions. To examine ovarian responses, 22-week-old C57BL/6J mice were exposed to simulated GCR and follicular development was assessed. Mice received 0 (control) or 5, 15, or 50 cGy of 5-ion simulated GCR and were euthanized either 14 or 126 days post-exposure. Ovaries were fixed, paraffin-embedded, serially sectioned to quantify follicular developmental stages (primordial to antral), determination of collagen content (i.e., ovarian fibrosis) and DNA damage. Serum anti-Müllerian hormone (AMH) concentrations were quantified by ELISA. At 14-days post-GCR, AMH levels did not differ between groups (averaging 260.6 ± 29.6 ng/ml). By 126-d post-GCR, the age-dependent decrease in AMH level was observed in control (177.3 ± 20.7) and 5 cGy (161.9 ± 29.6) when compared back to 14-d levels. In contrast, the 15 and 50 cGy animals had markedly reduced levels (100.1 ± 10.5 and 3.2 ± 0.8, respectively). At 14-days post-GCR, 5 cGy reduced secondary follicle numbers, while treatment with 15 and 50 cGy reduced primordial, primary, and secondary (preantral) follicles, while antral follicles remained similar across all groups. At 126-d post-GCR all doses of GCR impacted early follicular groups, with the 50 cGy causing a complete depletion at all stages. 14-d and 126-d post-GCR ovarian tissues exhibited dose-dependent increases in TUNEL + nuclei and collagen deposition, indicating early and sustained cellular damage and stromal remodeling, respectively. In conclusion, GCR-exposure impaired ovarian follicle development and health, causing premature depletion of the follicular reserve, which could lead to a shortened reproductive lifespan.