Molecular mechanisms regulating follicular recruitment and selection

Abstract

Ovarian follicular growth and development is an integrated process encompassing both extraovarian signals, such as gonadotrophins and metabolic hormones, and intraovarian factors. Follicular development has been classified into gonadotrophin-independent and -dependent phases. In the latter, FSH provides the primary drive for follicular recruitment and LH is required for continued development of follicles to the preovulatory stage. A transient increase in circulating FSH precedes the recruitment of a group of follicles, and these recruited follicles are characterized by expression of mRNAs encoding P450scc and P450arom in granulosal cells. As follicles mature, there is a transfer of dependency from FSH to LH, which may be part of the mechanism(s) involved in selection of follicles for continued growth. Indeed, changes in the pattern of expression of mRNA for gonadotrophin receptors and steroid enzymes within follicular cells appear to be closely linked to changes in peripheral concentrations of gonadotrophins. The mechanism of selection of dominant follicles still requires clarification, but seems to be linked to the timing of mRNA expression encoding LHr and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in granulosal cells. Additional intraovarian systems, including the ovarian IGF and activin/inhibin systems, also exert a role. For example, it appears that the development of follicular dominance in cows is associated with the FSH-dependent inhibition of the expression of mRNA encoding insulin-like growth factor binding protein 2 (IGFBP-2) in granulosal cells. In conclusion, the integration of these endocrine signals and intraovarian factors within follicles determines whether follicles continue to develop and become dominant or are diverted into apoptotic pathways leading to atresia.