Control of ovarian follicular development to the gonadotrophin-dependent phase: a 2006 perspective

In sheep, as in other mammals, ovarian follicular growth is regulated mainly by intraovarian growth factors during early development with pituitary hormones increasingly important during the final phases to ovulation. Most follicles are present as primordial structures and these express many hundreds of genes that fulfil an array of housekeeping and signalling functions. Once growth has been initiated, at least two oocyte-derived growth factors, namely growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), are critical for ongoing development to ovulation, most likely by regulating the proliferative and differentiative functions of adjacent follicular cells. In sheep, the granulosa cell populations double some 12-14 times and a well-defined thecal layer differentiates before antrum formation and the time taken to complete this process varies between 50 -150 days with very little follicular atresia. During preantral growth, FSH and LH receptors coupled to the cyclic AMP second messenger system develop in granulosa and thecal cells respectively. From the late preantral stage, GDF9, BMP15 and perhaps other factors are thought to regulate gene expression in cumulus cells to enhance metabolic cooperativity with the oocyte and in mural granulosa cells to regulate their responses to pituitary hormones. In sheep, antral follicular development is characterized by a much faster rate of growth, additional increases in the numbers of granulosa (4-5 more doublings) and thecal/cells, an increased level of steroid and inhibin secretion in response to FSH and LH, but also by most follicles undergoing atresia. The final number of follicles that go on to ovulate is dependent upon FSH as well as the intrafollicular concentrations of GDF9 and BMP15.