多囊卵巢综合征（PCOS）以排卵功能障碍、雄激素过多症和多囊卵巢形态为特征，影响着越来越多的育龄妇女。我们的研究旨在探讨外泌体 miR-4449 对颗粒细胞（GC）的分子机制和影响。两种永生化人卵巢颗粒细胞（KGN 和 COV434 细胞）用于体外功能研究。我们的研究发现，与对照患者相比，PCOS 女性的卵泡液 (FF) 来源的外泌体 miR-4449 显着减少。外泌体miR-4449可以减轻GCs氧化应激（OS）并促进GCs增殖，而抑制miR-4449表达后观察到相反的趋势。此外，我们通过双荧光素酶报告基因检测证明，Kelch 样 ECH 相关蛋白 1（KEAP1）是 miR-4449 的直接靶标，并且 PCOS FF 来源的外泌体中 KEAP1 和 miR-4449 的表达模式完全一致。对面的。此外，KEAP1/NRF2信号通路可能在GC增殖和OS中发挥重要作用。我们的结果表明，PCOS 中 FF 来源的外泌体 miR-4449 表达减少可能会加重 GC 的 OS，并通过 KEAP1/NRF2 信号通路抑制 GC 增殖。外泌体 miR-4449 可能是诊断 PCOS 的潜在生物标志物。我们的研究有助于对多囊卵巢综合征的发病机制有新的认识。

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Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovary morphology, affecting more and more women of reproductive age. Our study aimed to explore the molecular mechanism and effect of exosomal miR-4449 on granulosa cells (GCs). Two immortalized human ovarian granulosa cells (KGN and COV434 cells) were used for in vitro functional studies. Our study found that follicular fluid (FF) derived exosomal miR-4449 was significantly decreased in women with PCOS compared with the control patients. And exosomal miR-4449 could alleviate GCs oxidative stress (OS) and promote GCs proliferation, while the opposite trend was observed after inhibiting the expression of miR-4449. In addition, we demonstrated that Kelch-like ECH-associated protein 1(KEAP1) was a direct target of miR-4449 through dual-luciferase reporter assay, and the expression patterns of KEAP1 and miR-4449 in PCOS FF-derived exosomes were exactly opposite. In addition, KEAP1/NRF2 signaling pathway may play an important role in GCs proliferation and OS. Our results demonstrated that the decreased FF-derived exosomal miR-4449 expression in PCOS might aggravate the OS of GCs and inhibit GCs proliferation via KEAP1/NRF2 signaling pathway. Exosomal miR-4449 might be a potential biomarker for the diagnosis of PCOS. Our study contributes to a new understanding of the pathogenesis of PCOS.