Programmed cell death 4: A novel player in the pathogenesis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a pathological condition recognized by menstrual cycle irregularities, androgen excess, and polycystic ovarian morphology, affecting a significant proportion of women of childbearing age and accounting for the most prevalent cause of anovulatory sterility. In addition, PCOS is frequently accompanied by metabolic and endocrine disturbances such as obesity, dyslipidemia, insulin resistance, and hyperinsulinemia, indicating the multiplicity of mechanisms implicated in the progression of PCOS. However, the exact pathogenesis of PCOS is yet to be elucidated. Programmed cell death 4 (PDCD4) is a ubiquitously expressed protein that contributes to the regulation of various cellular processes, including gene expression, cell cycle progression, proliferation, and apoptosis. Despite some disparities concerning its exact cellular effects, PDCD4 is generally characterized as a protein that inhibits cell cycle progression and proliferation and instead drives the cell into apoptosis. The apoptosis of granulosa cells (GCs) is speculated to take a major part in the occurrence and progression of PCOS by ceasing antral follicle development and compromising oocyte competence. Given the possible involvement of GC apoptosis in the progression of PCOS, as well as the contribution of PDCD4 to the regulation of cell apoptosis and the development of metabolic diseases, the current review aimed to discuss whether or how PDCD4 can play a role in the pathogenesis of PCOS by affecting GC apoptosis. Significance statement: The present review discusses the potential role of programmed cell death 4 (PDCD4) in the pathogenesis of polycystic ovary syndrome (PCOS) by providing a link between its altered expression in granulosa cells (GCs) and the apoptosis of these cells. PDCD4 is a protein expressed ubiquitously and plays a significant role in regulating different cellular processes, such as apoptosis. The arrest of antral follicle development, as a leading disruption of follicular growth in PCOS, can result from the apoptosis of GCs. Hyperandrogenism‐induced PDCD4 dysregulation leads to upregulated PDCD4 expression, elevated GC apoptosis, and ultimately PCOS development. Accordingly, PDCD4 may serve as a possible target for the prognosis and alleviation of PCOS complications. [ABSTRACT FROM AUTHOR]