265. Increased FSH activity increases primordial follicle reserve and enhances preovulatory follicle survival in transgenic FSH female mice

Abstract

The mammalian female reproductive lifespan is determined by the depletion rate of the finite ovarian follicle reserve established before or shortly after birth. Follicle formation, initiation and early growth are thought to be independent of follicle-stimulating hormone (FSH), whereas antral follicle development requires FSH stimulation. Rising serum FSH is one of the earliest signs of reproductive ageing in women, coinciding with declining fecundity and an accelerated decline in remaining follicle reserves, but whether or not increased FSH plays a direct or feed-forward role in accelerating reproductive ageing remains undetermined. We previously described transgenic (Tg) mice with rising serum human FSH that produced larger litter sizes <20 weeks of age, then rapidly declining litter size from 20–40 weeks old (wo) culminating in premature infertility1. Despite declining fertility, ageing TgFSH females maintained ovulation rates ~3-fold higher than wt females. Follicle quantitation revealed that ovarian antral follicle numbers at diestrus were equivalent in 26 wo TgFSH and wt females. The elevated ovulation rates in TgFSH females may reflect increased preovulatory follicle survival during proestrus, as ~70% of large antral follicles go on to ovulate in TgFSH females, compared with only 30% in wt females. In contrast to the view that higher FSH may increase follicle development and consequently accelerate follicle depletion, examination of follicle reserve revealed that subfertile or infertile 26–52 wo TgFSH females exhibited increased total ovarian primordial follicle numbers (60%, P < 0.05) with no significant change in primary follicle numbers compared with age-matched wt females. Therefore, increased FSH activity appeared to act as a survival factor for primordial follicles. Our current analysis of increased FSH actions in female mice suggests that FSH may enhance the survival of both early (primordial) and late (preovulatory) follicle populations. (1) McTavish KJ et al. Endocrinology. 2007 Sep;148(9):4432–9.