New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2024-03-13 DOI:10.1007/s10735-024-10183-8

Peiwei Cong, Bing Shang, Lina Zhang, Zhaoli Wu, Yanan Wang, Jia Li, Lin Zhang

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Abstract

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

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治疗多囊卵巢综合征的新见解：HKDC1 通过调节线粒体功能和糖酵解促进卵巢粒细胞的生长

多囊卵巢综合征（PCOS）是一种内分泌疾病，其发病机制和治疗方法尚不清楚。Hexokinase domain component 1（HKDC1）参与调节线粒体功能和糖酵解。然而，它在多囊卵巢综合症发病过程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 毫克/千克体重）以建立多囊卵巢综合征的体内模型。在体外，使用人类卵巢颗粒细胞系 KGN 细胞来探索其潜在机制。经 DHEA 处理的小鼠表现出发情周期紊乱、激素水平异常和胰岛素抵抗。线粒体和糖酵解功能障碍是多囊卵巢综合征相关卵巢颗粒细胞生长抑制的主要原因。在这里，我们发现在HKDC1被沉默的KGN细胞中，线粒体结构受损，产生的ATP减少，线粒体活性氧产生增多。此外，HKDC1 基因敲除抑制了葡萄糖的消耗，减少了葡萄糖-6-磷酸和乳酸的产生。最终，HKDC1至少在一定程度上通过保护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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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.