The organelle oxidative-inflammatory network in polycystic ovary syndrome: from subcellular intercellular cascades to systemic comorbidities

Abstract

Polycystic ovary syndrome (PCOS) transcends localized reproductive dysfunction, manifesting as a systemic metabolic disorder driven primarily by insulin resistance (IR) and chronic inflammation. The condition was recently redesignated as polyendocrinometabolic syndrome (PMOS) to better reflect this systemic pathophysiology. (Note: This review retains the traditional PCOS nomenclature to maintain consistency with existing literature.) This review identifies the organelle oxidative network, characterized by mitochondrial dysfunction and endoplasmic reticulum (ER) stress, as a critical pathological nexus in PCOS progression. Lipotoxicity and glucotoxicity disrupt organelle homeostasis, precipitating macrophage metabolic reprogramming and diverse programmed cell death pathways, including ferroptosis and pyroptosis. Furthermore, the release of organelle-derived damage-associated molecular patterns (DAMPs) and extracellular vesicles amplifies localized metabolic insults into systemic cascades, exacerbating cardiovascular and glucolipid complications. We conclude by evaluating the therapeutic potential of targeting organelle defense systems and dissecting the deep cellular mechanisms of current metabolic agents, establishing a novel framework for PCOS diagnosis and clinical translation.