Abstract
Introduction
Long-duration Mars missions will expose female astronauts to galactic cosmic radiation (GCR), a deep-space radiation environment that cannot be fully shielded. Ovarian follicles are finite and highly susceptible to ionizing radiation, yet GCR’s effects on the ovary remain unknown. We hypothesize that GCR will negatively impact follicular development and ovulation.
Methods
GCRSim mimics the GCR encountered during Mars missions. Female Wistar rats were assigned to GCRSim/GCRSim (G/G, n=8) and Sham (n=8) treatment groups. Irradiated animals received 20 cGy of space radiation delivered in two doses separated by 6 months, sham animals received no radiation. Ovaries were collected during diestrus, embedded in paraffin, sectioned, and stained with H&E. Follicles were classified as primordial (squamous granulosa cells), primary (single cuboidal layer), secondary (multiple cuboidal layers), or antral (visible antrum). Follicle populations and corpora lutea were counted and analyzed. In a subset of five animals per group, secondary and antral follicles were assessed for mitotic figures and pyknotic nuclei as indicators of follicular proliferation and atresia. These animals were part of a study evaluating GCR effects on attentional set-shifting (ATSET) performance, which measures cognitive flexibility.
Results
G/G ovaries had fewer secondary follicles than Sham ovaries (p=0.048, Welch’s t-test). However, primordial, primary, and antral follicle counts were similar in both treatment groups. Sham ovaries contained more corpora lutea than G/G ovaries (p=0.046, Mann-Whitney U), and the proportion of ovaries lacking corpora lutea trended higher in the G/G group than in the Sham group (p=0.066, Fisher’s exact). Corpora lutea were present in 2/8 G/G ovaries and 6/8 Sham ovaries. G/G antral follicles had fewer mitotic figures than Sham follicles (p=0.028, Welch’s t-test), with a trend toward reduced mitosis in secondary follicles (p=0.061). G/G antral follicles had more pyknotic nuclei than Sham follicles (p=0.028, Welch’s t-test), with a trend toward increased pyknosis in secondary follicles (p=0.065). During the compound discrimination reversal (CDR) stage of the ATSET, which requires response updating following a change in learned contingencies, rats lacking corpora lutea took longer to make decisions than rats with corpora lutea (p=0.026).
Conclusion
GCRSim exposure reduced secondary follicle and corpora lutea counts, suggesting impaired follicular development and ovulation. Reduced mitotic activity and increased pyknosis in G/G follicles suggest that impaired follicular proliferation and increased atresia may contribute to reduced follicle development. Reduction of corpora lutea may decrease progesterone production and alter reproductive cycling, which is associated with early menopause, cardiovascular disease, osteoporosis, and early mortality. Additionally, absence of corpora lutea was associated with prolonged decision-making time. This suggests an association between ovarian function and cognitive flexibility following GCR exposure. Prolonged response times may be consequential during long-duration spaceflight, where timely decision-making and cognitive performance are critical to mission success. Further longitudinal studies are needed to determine whether these ovarian and cognitive changes are transient or permanent, and their implications for performance and female reproductive health after long-duration spaceflight.