Development of the dominant follicle: mechanisms of selection and maintenance of oocyte quality.

For a follicle to reach dominance, in mono-ovulatory species such as cattle, requires the integration of a number of processes involving both extra-ovarian signals and intra-follicular paracrine and autocrine regulators. Ovarian transplant studies in both cattle and sheep demonstrated that it takes approximately 4 months for primordial follicles to reach dominance. Gonadotrophins are not a prerequisite for the continued growth of pre-antral follicles, unlike antral follicles, but FSH does appear to stimulate development. Local growth factors, such as IGFs and BMPs, are expressed throughout follicle development and interact with gonadotrophins to stimulate development. As follicles become dominant, there is a transfer of dependency from FSH to LH. There are also differences in LH-responsiveness of theca and granulosa cells during follicular development, due to differential regulation and control by intricate local mechanisms altering LH receptor (LHR) mRNA expression. In addition, both the BMP and IGF systems can modulate the proliferative and differentiative responses of both granulosa and theca cells to gonadotrophins. There is a significant interaction between BMPs and the IGF system in regulating follicular development. A range of factors, including nutrition, will also determine the fate of the growing follicle and the quality of the oocyte. Nearly all follicles regress and apoptotic cell death throughout follicular development is an underlying mechanism of cell loss during follicular atresia. Several markers of follicular atresia have been identified including IGFBPs. There is a significant correlation between the presence of low molecular weight IGFBPs in bovine follicular fluid and caspase-3 activity of granulosa cells in individual follicles. In conclusion, it is the interaction between extra-ovarian and intra-ovarian factors that determine the fate of the follicle and the quality of the oocyte.