Early stress leads to effects on estrous cycle and differential responses to stress.

Women are more susceptible than men to stress-related mental disorders. However, few animal studies have been conducted on females. Given the interactions between gonadic hormones and the hypothalamo-pituitary-adrenal (HPA) axis, we hypothesized that the effects of early stress may be different between males and females depending on the state of their estrous cycle. Using adult Long-Evans rats of both genders, the effects of maternal deprivation were investigated on the estrous cycle length, corticosterone levels after food deprivation or restraint stress procedures, and the negative feedback efficiency of dexamethasone on the HPA axis. The individual length of the estrous cycle was evaluated using vaginal smears. Non-deprived (AFR) females mainly exhibited regular 5-day cycles (40% of the population) and 4-5-day cycles (26%), with fewer 4-day cycles (18%) and irregular cycles (16%). Comparatively, deprived (D) females displayed a significant decrease of 5-day cycles (24%) and a significant increase of irregular cycles (28%). After the restraint stress procedure, D females exhibited higher corticosterone level than AFR females during proestrous. After the food deprivation procedure, D and AFR females maintained dose-response sensitivity to the negative feedback induced by dexamethasone but only during proestrous. No differences were observed between D and AFR males under these experimental conditions. These data highlight the importance of early environmental factors in regulating the spontaneous pattern of the estrous cycle as well as gender- and stressor-dependent sensitivity of the HPA axis according to steroid levels.