Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation

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外文摘要：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.

外文关键词：

ovulationglutaminegranulosa cellsPCOSFSH

作者：

Kai-Hui Zhang、Fei-Fei Zhang、Zhi-Ling Zhang、Ke-Fei Fang、Wen-Xing Sun、Na Kong、Min Wu、Hai-Ou Liu、Yan Liu、Zhi Li、Qing-Qing Cai、Yang Wang、Quan-Wei Wei、Peng-Cheng Lin、Yan Lin、Wei Xu、Cong-Jian Xu、Yi-Yuan Yuan、Shi-Min Zhao

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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

School of Life Sciences and Institutes of Biomedical Sciences,Shanghai 2000438,China

Department of Nutrition and Food Hygiene,School of Public Health,Nantong University,Nantong 226019,China

Reproductive Medicine Center,The Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China

Department of Animal Science and Technology,Nanjing Agricultural University,Nanjing 210014,China

Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province,College of Pharmacy,Qinghai University for Nationalities,Xining 810007,China

Shanghai Fifth People's Hospital of Fudan University,Fudan University,Shanghai 200240,China

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基金：

State Key Development Programs of ChinaState Key Development Programs of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaProgram of Shanghai Academic Research LeaderChina postdoctoral science foundation

项目编号：

2018YFA08003002018YFA080130092253305318210023223005431930062918570009215700132171298819714498217167221XD14230002022M721954

出版年：

2024

DOI：

10.1093/procel/pwad065

蛋白质与细胞

CSTPCD

影响因子：0.645

ISSN：

年,卷(期)：2024.15(7)