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Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation

摘要:

Polycystic ovary syndrome(PCOS)is the leading cause of anovulatory infertility.Inadequate understanding of the ovulation drivers hinders PCOS intervention.Herein,we report that follicle stimulating hormone(FSH)controls follicular fluid(FF)glutamine levels to determine ovulation.Murine ovulation starts from FF-exposing granulosa cell(GC)apoptosis.FF glutamine,which decreases in pre-ovulation porcine FF,elevates in PCOS patients FF.High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal,metabolic,and mor-phologic PCOS traits.Mechanistically,follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine,which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apop-totic pathway.FSH and glutamine inhibit the rapture of cultured murine follicles.Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO.These suggest that glutamine,FSH,and ASK1-JNK pathway are targetable to alleviate PCOS.

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作者: Kai-Hui Zhang [1] Fei-Fei Zhang [2] Zhi-Ling Zhang [3] Ke-Fei Fang [2] Wen-Xing Sun [4] Na Kong [5] Min Wu [5] Hai-Ou Liu [2] Yan Liu [2] Zhi Li [2] Qing-Qing Cai [2] Yang Wang [2] Quan-Wei Wei [6] Peng-Cheng Lin [7] Yan Lin [8] Wei Xu [9] Cong-Jian Xu [2] Yi-Yuan Yuan [8] Shi-Min Zhao [10]
作者单位: The Obstetrics & Gynecology Hospital of Fudan University,State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200090,China;Shanghai Key Laboratory of Metabolic Remodeling,and Children's Hospital of Fudan University,Shanghai 200032,China;Pediatric Research Institute,Children's Hospital Affiliated to Shandong University(Jinan Children's Hospital),Jinan 250022,China [1] The Obstetrics & Gynecology Hospital of Fudan University,State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200090,China [2] The Obstetrics & Gynecology Hospital of Fudan University,State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200090,China;Shanghai Key Laboratory of Metabolic Remodeling,and Children's Hospital of Fudan University,Shanghai 200032,China;School of Life Sciences and Institutes of Biomedical Sciences,Shanghai 2000438,China [3] Department of Nutrition and Food Hygiene,School of Public Health,Nantong University,Nantong 226019,China [4] Reproductive Medicine Center,The Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China [5] Department of Animal Science and Technology,Nanjing Agricultural University,Nanjing 210014,China [6] Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province,College of Pharmacy,Qinghai University for Nationalities,Xining 810007,China [7] The Obstetrics & Gynecology Hospital of Fudan University,State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200090,China;Shanghai Key Laboratory of Metabolic Remodeling,and Children's Hospital of Fudan University,Shanghai 200032,China [8] The Obstetrics & Gynecology Hospital of Fudan University,State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200090,China;Shanghai Key Laboratory of Metabolic Remodeling,and Children's Hospital of Fudan University,Shanghai 200032,China;Shanghai Fifth People's Hospital of Fudan University,Fudan University,Shanghai 200240,China [9] The Obstetrics & Gynecology Hospital of Fudan University,State Key Laboratory of Genetic Engineering,Fudan University,Shanghai 200090,China;Shanghai Key Laboratory of Metabolic Remodeling,and Children's Hospital of Fudan University,Shanghai 200032,China;School of Life Sciences and Institutes of Biomedical Sciences,Shanghai 2000438,China;Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province,College of Pharmacy,Qinghai University for Nationalities,Xining 810007,China [10]
期刊: 《蛋白质与细胞》2024年15卷7期 512-529页 SCIMEDLINEISTICCSCDBP
栏目名称: RESEARCH ARTICLES
DOI: 10.1093/procel/pwad065
发布时间: 2024-07-29
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