Folliculogenesis and Abnormalities

Abstract

Research on oocytes and their associated follicles has advanced significantly over the past two decades, shedding light on the fragility of the processes governing their active life. The ovarian follicles and the germ cells within them are crucial to understand conception, growth, and survival mechanisms. Folliculogenesis, the process by which ovarian follicles develop, starts with the primordial follicle, which contains oocytes arrested in meiotic division. These follicles are crucial for the ovarian reserve and serve as the sole source of oocytes throughout a woman’s life. Follicle maturation is regulated by a series of biochemical signals involving granulosa and theca cells, as well as hormones like FSH and AMH. This process begins during fetal development and continues until menopause, with primordial follicles being activated and transitioning into primary follicles. Each stage of follicular maturation is linked to meiotic events that drive the oocyte’s progressive development. Despite the continuous loss of primordial follicles, these cells retain autocrine and paracrine factors that regulate their activation, promoting oocyte growth and supporting both spontaneous and assisted reproduction. The early stages of folliculogenesis involve critical signaling pathways and growth factors such as mTOR, PI3K, and Hippo, which regulate follicle development even before gonadotropin involvement. Initially, follicular growth is influenced by local growth factors like activins and AMH, with gonadotropins playing a larger role as the follicle progresses. Follicles develop through four stages—primary, secondary, tertiary, and Graafian—each regulated by intra-ovarian mechanisms. Oocytes also actively contribute to folliculogenesis by secreting growth factors that interact with granulosa and theca cells. As follicles grow, the oocyte is suspended in follicular fluid and surrounded by granulosa cells forming a structure called the corona radiata. Meiosis begins in fetal life but is arrested until puberty when it resumes just before ovulation. However, not all oocytes will be ovulated; many undergo atresia through apoptosis. Abnormalities in signaling pathways or follicle development can lead to reproductive disorders, highlighting the importance of understanding the molecular mechanisms involved in ovarian function.