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.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- PCOS:
-
Polycystic ovary syndrome
- GEO:
-
Gene expression omnibus
- GCs:
-
Granulosa cells
- GO:
-
Gene ontology
- KEGG:
-
The Kyoto encyclopedia of genes and genomes
- BP:
-
Biological processes
- CC:
-
Cellular components
- MF:
-
Molecular functions
- ATP:
-
Adenosine triphosphate
- rt-qPCR:
-
Real-time quantitative polymerase chain reaction
- IF:
-
Immunofluorescence
- BCA:
-
Bicinchoninic acid
- ROS:
-
Reactive oxygen species
- LH:
-
Luteinizing hormone
- FSH:
-
Follicle stimulating hormone
- HOMA-IR:
-
Homeostatic model assessment of insulin resistance
- G6P:
-
Glucose-6-phosphate
- MMP:
-
Mitochondrial membrane potential
- EdU:
-
Ethynyl deoxyuridine
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Funding
This study was funded by the Youth Project of National Natural Science Foundation of China (No. 82104735), the 71st Batch of General Program of China Postdoctoral Science Foundation “Regional Special Support Program” (No. 2022MD713764), Open Fund of Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine (No. zyzx2202), the Basic Scientific Research Project of the Educational Department of Liaoning Province (No. JYTMS20231815).
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Writing—original draft preparation: Peiwei Cong and Bing Shang; Methodology, Formal analysis and investigation: Lina Zhang, Zhaoli Wu, and Yanan Wang; Methodology and Resources: Jia Li; Writing—review and editing, Funding acquisition, and Supervision: Lin Zhang.
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Cong, P., Shang, B., Zhang, L. et al. New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis. J Mol Histol 55, 187–199 (2024). https://doi.org/10.1007/s10735-024-10183-8
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DOI: https://doi.org/10.1007/s10735-024-10183-8