Abstract
Introduction
NASA’s planned Mars missions will result in astronaut exposure to galactic cosmic rays (GCR) on both the outbound and return journeys. GCR may harm the female reproductive system which is uniquely susceptible to damage. Damage to the ovary may reduce fertility and induce early menopause, increasing risk for cardiovascular disease, osteoporosis, and early death for female astronauts. Altered ovarian function may also impact decision-making by female astronauts. We hypothesize that GCR will harm rat ovaries leading to reduced corpora lutea development, follicle loss, and follicle damage.
Methods
Female Wistar rats were exposed to no irradiation (sham) or exposed to 20 cGy of simulated GCR (G/G) delivered in two doses separated by 6 months. At 4 months after the last exposure, rats were euthanized in diestrus. Ovaries from sham and G/G exposed rats were embedded in paraffin, sectioned, and every 5th was stained with H&E. Corpora lutea and follicles were manually counted. Corpora lutea counts was assessed by Mann-Whitney U Test. Follicles were categorized as primordial, primary, secondary, or antral based on surrounding granulosa cells and compared using one tailed t-test. Pyknosis and mitosis were assessed by counting pyknotic and mitotic nuclei in secondary and antral follicles and compared using one tailed t-test.
Results
While 75% of sham rats showed signs of active ovulation (containing >11 corpora lutea), only 17% of G/G exposed ovaries had comparable corpora luteal numbers, with the rest containing no corpora lutea. An inter-group comparison revealed significantly fewer corpora lutea within the ovaries of GCR exposed rats than in those from sham rats (p=0.046). GCR exposure reduced the number of secondary follicles (p=0.048), but not follicles at other stages (p>0.05). There was a significant increase in pyknotic nuclei (p=0.028) and significant decrease in mitotic nuclei (p=0.028) in antral follicles exposed to GCR. These rats were part of a study that established the impact of GCR exposure on decision making (attentional set-shifting, ATSET) performance. During the compound discrimination reversal (CDR) stage of that task, rats without corpora lutea took significantly (P=0.026) longer to make decisions when compared to rats with corpora lutea.
Conclusion
Our results showed that low dose GCR exposure resulted in decreased corpora luteal, indicating that GCR exposed rats were not actively ovulating. This is consistent with a disruption of LH signaling following GCR exposure, suggesting that the hypothalamus may be radiosensitive. Our results also showed a significant loss in follicles at the secondary stage along with an increase in pyknosis and decrease in mitosis at the antral stage, consistent with radiation-induced follicle damage. There was a correlation between the ovulation status (presence or absence of corpora lutea) and processing speed in the CDR task (ATSET). Overall, space radiation is damaging to the structure of the ovary, with likely consequences for both ovarian function and executive performance. Should similar effects occur in humans, GCR exposure during the mission to Mars could lead to early menopause in female astronauts, and the associated clinical conditions.