Polycystic ovary syndrome (PCOS) is an endocrine disease, and its pathogenesis and treatment are still unclear. Hexokinase domain component 1 (HKDC1) participates in regulating mitochondrial function and glycolysis. However, its role in PCOS development remains unrevealed. Here, female C57BL/6 mice were intraperitoneally injected with dehydroepiandrosterone (DHEA; 60 mg/kg body weight) to establish an in vivo model of PCOS. In vitro, KGN cells, a human ovarian granular cell line, were used to explore the potential mechanisms. DHEA-treated mice exhibited a disrupted estrus cycle, abnormal hormone levels, and insulin resistance. Dysfunction in mitochondria and glycolysis is the main reason for PCOS-related growth inhibition of ovarian granular cells. Here, we found that the structure of mitochondria was impaired, less ATP was generated and more mitochondrial Reactive Oxygen Species were produced in HKDC1-silenced KGN cells. Moreover, HKDC1 knockdown inhibited glucose consumption and decreased the production of glucose-6-phosphate and lactic acid. Conclusively, HKDC1 protects ovarian granulocyte cells from DHEA-related damage at least partly by preserving mitochondrial function and maintaining glycolysis.

Graphical abstract

中文翻译：

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多囊卵巢综合征治疗新见解：HKDC1通过调节线粒体功能和糖酵解促进卵巢粒细胞生长

多囊卵巢综合征（PCOS）是一种内分泌疾病，其发病机制和治疗尚不清楚。己糖激酶结构域成分 1 (HKDC1) 参与调节线粒体功能和糖酵解。然而，它在 PCOS 发展中的作用仍未被揭示。在这里，雌性C57BL/6小鼠腹腔注射脱氢表雄酮（DHEA；60 mg/kg体重）以建立PCOS体内模型。在体外，使用人卵巢颗粒细胞系 KGN 细胞来探索其潜在机制。DHEA 治疗的小鼠表现出发情周期中断、激素水平异常和胰岛素抵抗。线粒体和糖酵解功能障碍是 PCOS 相关的卵巢颗粒细胞生长抑制的主要原因。在这里，我们发现 HKDC1 沉默的 KGN 细胞中线粒体结构受损，产生的 ATP 减少，产生更多的线粒体活性氧。此外，HKDC1 敲除抑制了葡萄糖消耗并减少了 6-磷酸葡萄糖和乳酸的产生。总之，HKDC1 至少部分通过保留线粒体功能和维持糖酵解来保护卵巢粒细胞免受 DHEA 相关损伤。

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