Polycystic ovary syndrome: The role of granulosa cell proliferation and apoptosis in disease development

Abstract

Polycystic ovary syndrome (PCOS) is the most prevalent ovarian endocrine disorder in infertile women and significantly impacts their health. Granulosa cell (GC) is the largest functional cell type in follicular development and plays a crucial role in follicle growth, differentiation, and maturation. Studies have shown that women with PCOS experience abnormal GC proliferation and apoptosis, which contribute to symptoms such as inflammation, irregular estrous cycles, hormonal imbalances, and follicular development arrest. These findings suggest that altered GC quantity is a key factor in the pathogenesis and progression of PCOS. Nevertheless, substantial inconsistencies exist in studies regarding GC number changes in PCOS follicles. To explore the underlying causes, we reviewed recent literature on GC proliferation and apoptosis in PCOS over the past years. This review identifies several potential causes contributing to these discrepancies, including overlooked follicular-phase-dependent effects on GC quantity, variations in GC sources (PCOS vs. non-PCOS, human vs. animal models, and human immortalized granulosa cells), and the lack of animal model validation, inadequate detection of relevant indicators, and unclear identification of vital influential factors. To address these issues, we propose several potential solutions to provide valuable insights into elucidating the roles of GC proliferation and apoptosis, their regulatory mechanisms, and potential therapeutic strategies in PCOS.