Fig. 6.

Upregulation of cell death pathways in polycystic ovary syndrome (PCOS). The diagram unifies the heightened programmed cell death pathways (apoptosis, necroptosis, and pyroptosis) in PCOS pathogenesis and their effects on ovarian function. Apoptosis (↑): Enhanced apoptosis of granulosa cells (GCs) leads to impaired oocyte maturation, reduced fertilization, and poor pregnancy outcomes. Necroptosis (↑): Inflammation stimulates necroptosis in GCs by mechanisms involving RIP kinases and necroptosis-related genes such as IL-33, BCL2, PYMG, and TNFSF10. This mechanism results in granulosa cell injury and ovarian dysregulation. The therapeutic agents such as resveratrol, quercetin, tretinoin, and curcumin have been implicated to modulate necroptosis and inflammation in PCOS. Pyroptosis (↑): Hyperandrogenism induces NLRP3 inflammasome activation, which leads to increased caspase-1 and IL-1β release, increased inflammation, and fibrosis of the ovaries, thereby decreasing ovarian function. Overactivation of pyroptosis generates a feedback loop that sustains inflammation and ovarian damage. Together, these dysregulated cell death mechanisms are causally responsible for the inflammatory and fibrotic processes that result in the reproductive and metabolic aberrations of PCOS