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

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...

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Veröffentlicht in:Journal of molecular histology 2024-04, Vol.55 (2), p.187-199
Hauptverfasser: Cong, Peiwei, Shang, Bing, Zhang, Lina, Wu, Zhaoli, Wang, Yanan, Li, Jia, Zhang, Lin
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container_issue 2
container_start_page 187
container_title Journal of molecular histology
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creator Cong, Peiwei
Shang, Bing
Zhang, Lina
Wu, Zhaoli
Wang, Yanan
Li, Jia
Zhang, Lin
description 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
doi_str_mv 10.1007/s10735-024-10183-8
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subjects Biomedical and Life Sciences
Biomedicine
Body weight
Cell Biology
Dehydroepiandrosterone
Developmental Biology
Endocrine disorders
Estrus cycle
Glycolysis
Granulocytes
Hexokinase
Insulin resistance
Leukocytes (granulocytic)
Life Sciences
Mitochondria
Original Paper
Ovaries
Polycystic ovary syndrome
Reactive oxygen species
title New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis
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