Increasing Blunting of Inhibin Responses to Dynamic Ovarian Challenge Is Associated With Reproductive Aging in the Rat

Abstract

Reproductive aging results in declines in female fertility and in slight declines in baseline serum inhibins in humans. The authors tested the hypothesis that exogenous ovarian stimulation as a noninvasive dynamic test, by amplifying inhibin levels, can define more accurately than baseline serum inhibin levels the ovarian age of female rats. Female rats—young (immature, 26 days old), adult (65-75 days old), and reproductively aged (8- to 9-month-old retired breeders)—were administered pregnant mare's serum gonadotropin to stimulate the ovaries and the serum inhibin A and inhibin B, and ovarian inhibins were measured. The young and adult females had at least a 4- to 10-fold increase in serum inhibin A and inhibin B after ovarian stimulation, but the reproductively aged females did not. Adult female serum inhibin measurements after stimulation at every stage of the estrous cycle revealed a consistent 4- to 5-fold increase in all stages, whereas the reproductively aged females did not. Western blot analyses of ovarian lysates were consistent with the serum inhibin level results and revealed that ovarian inhibin α, inhibin β A, and inhibin β B subunit levels in adult ovaries were elevated after ovarian stimulation but not in the reproductively aged ovaries. The data presented here demonstrate that young, adult, and reproductively aged female inhibin responses after exogenous ovarian stimulation were different. Inhibin measurement in serum after ovarian challenge in rats, therefore, is a noninvasive method that could be used to dissect ovarian function in aging in more detail.