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In multiparous rats, the incidence of regular estrous cyclicity and fertility decreases markedly at middle age. However, recent studies have shown that repeated pregnancies or progesterone (P) implants can subsequently cause retired breeder females to maintain regular cyclicity for an extended period of time; these results suggest a P-mediated deceleration of reproductive aging. In the present study, we examined the relation of ovarian steroid levels in young virgin females to their subsequent estrous cyclicity and reproductive function during aging as compared to multiparous females. Beginning at 4 mo of age and continuing to 6 mo of age, regularly cyclic virgin rats received either consecu-tive P implants (n=41) or no implants (controls, n=45) for 3 wk, followed by implant removal for 1 wk. Addi-tional females (n=72) were mated and allowed to undergo repeated pregnancies at 4, 6½, and 8 mo of age. Blood samples were obtained tbrougbout the estrous cycle (virgin females), during pregnancy (multiparous rats), and on Day 11 of successive treatments with P implants (virgins with P implants) for P, estradiol (E2), and testosterone (T) measurements. Subsequently, regularly cyclic females from all three groups were mated with fertile males to undergo term pregnancies at 10 and 12 mo of age. While the virgin controls showed cyclic increases in P, T, and E2 secretion during their estrous cycles, the P-implanted females had persistently low E2 and high P and T levels during treatment, which indicates an inhibition of ovarian E2 synthesis by P. In the virgin controls, the incidence of regular cyclicity was 62%, 51%, and 31% at 6½, 8, and 10 mo of age. However, among these regularly cyclic, virgin females, only 29% and 11% bad fertile gestations at 10 and 12 mo of age, respectively. In contrast, the incidence of regular cyclicity in the P-implanted virgins was 85%, 85%, and 51% at each corresponding age similar to those observed in the multiparous group (94%, 94%, and 72%). Moreover, among these regularly cyclic females previously implanted with P, 79% and 39% bad fertile gestations at 10 and 12 mo of age, significantly (p<0.05) greater than those observed in the multiparous group (45% and 16%) and in the virgin controls. These findings demonstrate that P implants in young virgin rats decrease the ovarian synthesis of E2 and result in the subsequent maintenance of regular estrous cyclicity and improved reproductive function at middle age.
LaPolt et al. (Mon,) studied this question.