Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder in women of reproductive age, marked by hyperandrogenism, ovulatory dysfunction, and insulin resistance, accompanied by significant metabolic disturbances, including glycolytic dysfunction, mitochondrial impairment, and increased oxidative stress. In granulosa cells (GCs), disrupted glycolysis impairs follicular development and compromises oocyte quality, exacerbating reproductive and metabolic abnormalities. At the molecular level, dysregulated energy-sensing pathways, such as AMPK and mTOR, reduce glucose uptake, lower ATP generation, and enhance oxidative stress, fueling disease progression. Epigenetic changes and non-coding RNAs further modulate glycolytic enzyme expression, destabilizing metabolic homeostasis within ovarian follicles. Therapeutically, restoring glycolytic balance using agents like metformin, resveratrol, mogroside V, and nicotinamide mononucleotide (NMN) has shown promise in improving glycolysis, insulin sensitivity, and ovarian function in various models. This review synthesizes current evidence on glycolysis's critical role in PCOS pathophysiology, its influence on follicular energetics and oocyte quality, and highlights metabolic targets for future therapies, offering a foundation for novel mechanism-driven interventions in PCOS management.
Keywords: glycolysis; granulosa cells; insulin resistance; metabolic dysfunction; metabolic therapy; oxidative stress; polycystic ovary syndrome.
© 2025 Cao et al.