Influences of age and reproductive status on ovarian ovulatory responsiveness to gonadotropin stimulation

Reproductive aging in the female rat is associated with the gradual loss of regular ovulatory function, decreased fertility, and smaller litter sizes. In the present study, we assessed ovarian ovulatory responsiveness to exogenous gonadotropin stimulation in young and middle-aged cyclic females and in middle-aged acyclic persistent-estrous (PE) rats. The ovulatory response to human chorionic gonadotropin (hCG) was dose-dependent in both young and middle-aged cyclic rats, with the percentages of rats ovulating and the numbers of ova shed per rat increasing with the dose of hCG administered. At the highest dose tested (10 mIU hCG/g bw), the range in ovulation rates among middle-aged cyclic rats (0-18 ova shed/rat) was greater than that in young animals (12-18 ova/rat). However, there were no statistically significant differences in either the percentages of females ovulating or in the mean ovulation rates between young and middle-aged cyclic groups. In contrast to the normal ovulatory responses observed in most middle-aged cyclic animals, response to hCG was markedly impaired in PE females of the same age. Middle-aged PE rats consistently failed to ovulate in response to a dose of hCG (10 mIU/g bw), which elicited high ovulation rates in young rats. At an even higher dose (20 mIU/g bw), only minimal ovulatory responses were observed (1.8 +/- 0.8 ova/rat; 80% of rats ovulating). Thus, most middle-aged regularly cyclic females maintain a similar ovulatory responsiveness to hCG as young rats, suggesting that decreased ovulation rates during aging may be related to attenuated preovulatory LH surges. However, impaired ovulatory responses were observed in middle-aged PE females, indicating altered ovarian function in acyclic animals, which may contribute to their anovulatory state.