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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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.
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doi_str_mv | 10.1007/s10735-024-10183-8 |
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Graphical abstract</description><identifier>ISSN: 1567-2379</identifier><identifier>EISSN: 1567-2387</identifier><identifier>DOI: 10.1007/s10735-024-10183-8</identifier><identifier>PMID: 38478190</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>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</subject><ispartof>Journal of molecular histology, 2024-04, Vol.55 (2), p.187-199</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Nature B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-b3e6b39c89a765e9d3dc2ae03813b56be78f95dcd0d67f5abca546f9c9bcefe83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10735-024-10183-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10735-024-10183-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38478190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cong, Peiwei</creatorcontrib><creatorcontrib>Shang, Bing</creatorcontrib><creatorcontrib>Zhang, Lina</creatorcontrib><creatorcontrib>Wu, Zhaoli</creatorcontrib><creatorcontrib>Wang, Yanan</creatorcontrib><creatorcontrib>Li, Jia</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><title>New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis</title><title>Journal of molecular histology</title><addtitle>J Mol Histol</addtitle><addtitle>J Mol Histol</addtitle><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</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Body weight</subject><subject>Cell Biology</subject><subject>Dehydroepiandrosterone</subject><subject>Developmental Biology</subject><subject>Endocrine disorders</subject><subject>Estrus cycle</subject><subject>Glycolysis</subject><subject>Granulocytes</subject><subject>Hexokinase</subject><subject>Insulin resistance</subject><subject>Leukocytes (granulocytic)</subject><subject>Life Sciences</subject><subject>Mitochondria</subject><subject>Original Paper</subject><subject>Ovaries</subject><subject>Polycystic ovary syndrome</subject><subject>Reactive oxygen species</subject><issn>1567-2379</issn><issn>1567-2387</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kU2P1SAUhonROB_6B1wYEjduqlBaPtyZq-MYJ7rRNaH0tJdJC1egM-k_8mdK545j4sIVB3jO-x54EXpByRtKiHibKBGsrUjdVJRQySr5CJ3SlouqZlI8fqiFOkFnKV0TUkveqKfohMlGSKrIKfr1FW6x88mN-5xKkQPOe8A5gskz-IzDgA9hWu2asrM43Ji44rT6PoYZ3uHLLx92FB_KJmRId61jDLd5v_VtsDO-nBi_TMGuGbCFaUq4W3GEcZlMdn7Es8vB7kPRdGbCw-JtdsFj43s8Fufinlx6hp4MZkrw_H49Rz8uPn7fXVZX3z593r2_qiyrea46BrxjykplBG9B9ay3tQHCJGVdyzsQclBtb3vSczG0prOmbfigrOosDCDZOXp91C2P-rlAynp2aZvaeAhL0rVqBeVMqg199Q96HZboy3SaEUYbwRrWFqo-UjaGlCIM-hDdXL5RU6K3HPUxR11y1Hc56k365b300s3QP7T8Ca4A7AikcuVHiH-9_yP7G_JCrcw</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Cong, Peiwei</creator><creator>Shang, Bing</creator><creator>Zhang, Lina</creator><creator>Wu, Zhaoli</creator><creator>Wang, Yanan</creator><creator>Li, Jia</creator><creator>Zhang, Lin</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20240401</creationdate><title>New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis</title><author>Cong, Peiwei ; Shang, Bing ; Zhang, Lina ; Wu, Zhaoli ; Wang, Yanan ; Li, Jia ; Zhang, Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-b3e6b39c89a765e9d3dc2ae03813b56be78f95dcd0d67f5abca546f9c9bcefe83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Body weight</topic><topic>Cell Biology</topic><topic>Dehydroepiandrosterone</topic><topic>Developmental Biology</topic><topic>Endocrine disorders</topic><topic>Estrus cycle</topic><topic>Glycolysis</topic><topic>Granulocytes</topic><topic>Hexokinase</topic><topic>Insulin resistance</topic><topic>Leukocytes (granulocytic)</topic><topic>Life Sciences</topic><topic>Mitochondria</topic><topic>Original Paper</topic><topic>Ovaries</topic><topic>Polycystic ovary syndrome</topic><topic>Reactive oxygen species</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cong, Peiwei</creatorcontrib><creatorcontrib>Shang, Bing</creatorcontrib><creatorcontrib>Zhang, Lina</creatorcontrib><creatorcontrib>Wu, Zhaoli</creatorcontrib><creatorcontrib>Wang, Yanan</creatorcontrib><creatorcontrib>Li, Jia</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular histology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cong, Peiwei</au><au>Shang, Bing</au><au>Zhang, Lina</au><au>Wu, Zhaoli</au><au>Wang, Yanan</au><au>Li, Jia</au><au>Zhang, Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis</atitle><jtitle>Journal of molecular histology</jtitle><stitle>J Mol Histol</stitle><addtitle>J Mol Histol</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>55</volume><issue>2</issue><spage>187</spage><epage>199</epage><pages>187-199</pages><issn>1567-2379</issn><eissn>1567-2387</eissn><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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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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