From Ovarian Development to Folliculogenesis: Essential Networks Sustaining the Ovarian Reserve

In the last four decades, transgenic and knockout mouse models have helped to understand the mechanisms of mammalian sex determination, germ cell development, and adult gonad functions. We have gained crucial insights into molecular factors and pathways of the cells generating either the supporting gonadal cells or germ cells of both sexes. In this review, we highlighted some of the main gene networks and regulatory mechanisms involved in the plasticity of sex-determining pathways that help to establish a functional ovary that can nurture the follicles to generate a good ovarian reserve, both in quantity and quality. Although this level of plasticity is still found in the fully differentiated gonads, errors like mutations or epigenetic modifications impact ovarian development and, later, folliculogenesis, resulting in infertility. To highlight some adverse reproductive outcomes associated with perturbations at the molecular and cellular levels in human folliculogenesis, two examples, i.e., Polycystic Ovary Syndrome (PCOS) and Premature Ovarian Insufficiency (POI), were selected and briefly discussed in this review.