Control of growth and development of preantral follicle: insights from in vitro culture

The regulation of folliculogenesis involves a complex interaction among endocrine, paracrine and autocrine factors. The mechanisms involved in the initiation of the growth of the primordial follicle, i.e., follicular activation and the further growth of primary follicles up to the pre-ovulatory stage, are not well understood at this time. The present review focuses on the regulation and development of early stage (primordial, primary, and secondary) folliculogenesis highlighting the mechanisms of primordial follicle activation, growth of primary and secondary follicles and finally transition from secondary to tertiary follicles. We also discuss the importance of in vitro follicle culture for the understanding of folliculogenesis during the preantral phase. Studies suggest that follicular development from primordial to early antral stages is primarily controlled by intra-ovarian ligands but it can also be influenced by many extra-ovarian factors. The control of early folliculogenesis is, therefore, extremely complex because several ligands act through distinct signaling pathways that form sophisticated information networks responding to multiple, often opposing, stimuli. The balance among different stimuli determines follicular survival or death as well as quiescence or activation (growth). The distribution of the ligands and their corresponding receptors varies among follicular compartments and species, and significant changes in gene expression pattern among follicular categories have been reported. Knowing that follicular requirements during early folliculogenesis can be stage-specific and species-specific, in vitro culture studies offer an alternative to evaluate single and combined factors during a specific period of follicular development. Herewith we summarize the main findings obtained in vitro together with the mechanisms regulating folliculogenesis.