Mechanisms of follicle selection and development.

Follicle recruitment and selection, the process that gives rise to the dominant follicle (DF) and the physiological state of the DF are important areas of research. The selection of a single ovarian follicle for further differentiation and finally ovulation is a shared phenomenon in monovulatory species including humans. The DF is different from other follicles because it can escape atresia (the fate of all other follicles). The DF cells develop corpus luteum if exposed to the luteinizing hormone (LH) surge. Several mechanisms for DF selection have been proposed. Rising follicle stimulating hormone (FSH) concentrations induce the emergence of a follicle wave and cohort attrition occurs during declining FSH concentrations, resulting in DF selection. Cohort secretions are initially responsible for the decline in FSH, which is subsequently suppressed by the selected DF lowering it below the threshold of FSH requirements of all other cohort follicles. The DF acquires relative FSH-independence in order to continue growth and differentiation during further declining FSH concentrations. A transition from FSH- to LH-dependence is postulated as the mechanism for the continued development of the selected DF. In addition, FSH and insulin-like-growth factor (IGF) enhance each other's ability to stimulate follicle cell function. Access of IGF II to their receptors is regulated by IGF binding proteins that are in turn regulated by specific proteases; all of which have been ascribed a role in DF development. One other shared mechanism recently proposed for DF selection is the possible differential regulation of blood vessel formation. Anti-Mullerian hormone (AMH) also plays a critical role in selection of the DF. AMH levels decline as the size of the follicle increases. Once follicles reach a size at which they are dominant, it has largely disappeared. From the time a follicle has been selected, the follicle destined to ovulate greatly enlarges and shows marked changes in its steroidogenic activity. LH surge causes a significant decline in gap junctions leading to dissociation of mural granulosa cells (GC) and expansion of the cumulus-oocyte complex (COC). The oocyte resumes its meiosis and progresses from prophase 1 to metaphase 2 at the time of ovulation. The concept of DF selection could be applied to the in-vitro maturation (IVM) program. Understanding the mechanism of DF selection in menstrual cycles is the key to planning the optimal timing of oocyte retrieval in order to obtain competent oocytes and embryos. Although the timing of oocyte retrieval is still open to debate, there is evidence to suggest that it may be better to retrieve oocytes before the small cohort follicles complete the process of atresia following selection of the DF.