125. ELEVATED FSH INCREASES PRIMORDIAL FOLLICLE RESERVE WITHOUT INCREASING PRIMORDIAL FOLLICLE FORMATION OR DECREASING OOCYTE QUALITY

Declining ovarian follicle reserve and oocyte quality with age can dictate the mammalian female reproductive lifespan. Elevated circulating levels of follicle-stimulating hormone (FSH) coincides with reproductive ageing in women, and is predicted to accelerate the depletion of ovarian follicle reserve by increasing the recruitment of remaining follicles. Unexpectedly, we found that transgenic expression of human FSH (TgFSH) increased primordial follicle reserve in mature GnRH-deficient hypogonadal (hpg) female mice functionally lacking endogenous gonadotrophin secretion1. Advancing our finding of increased primordial reserve in TgFSH-hpg mice, we find that total primordial follicle numbers is significantly increased (60%) in mature 26 week old non-hpg TgFSH females compared to WT controls. Thus, the FSH-induced increase in primordial reserve is maintained despite increased ovulation rate2 in mature TgFSH females. Embryo transfer experiments showed that embryos derived from 26 week old TgFSH females developed normally in recipient WT females, indicating no significant reduction in the viability of oocytes or early embryos produced by TgFSH mice. In addition, equal primordial numbers in 5 day old TgFSH versus WT ovaries suggested that FSH-induced changes to ovarian reserve was not due to an increased initial primordial follicle pool. Initial analysis of postnatal gene expression (qPCR) found elevated expression of granulosa cell markers (Kit-L, inhibin β) in TgFSH-hpg vs non-Tg hpg ovaries, indicating FSH actions during early follicle development. Therefore, contrary to a classical view that preantral follicles are gonadotrophin-independent, we provide in vivo evidence demonstrating FSH-induced changes to early follicle populations, as well as elevated FSH activity increasing or maintaining primordial reserve without compromising oocyte quality. (1) Allan CM et al. J Endocrinol. 2006; 188(3): 549–57.(2) McTavish KJ et al. Endocrinology. 2007; 148(9): 4432–9.