Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.,Protein & Cell

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Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.
Protein & Cell ( IF 13.6 ) Pub Date : 2024-07-01 , DOI: 10.1093/procel/pwad065
Kai-Hui Zhang _{1,

2,

3} , Fei-Fei Zhang ₁ , Zhi-Ling Zhang _{1,

2,

4} , Ke-Fei Fang ₁ , Wen-Xing Sun ₅ , Na Kong ₆ , Min Wu ₆ , Hai-Ou Liu ₁ , Yan Liu ₁ , Zhi Li ₁ , Qing-Qing Cai ₁ , Yang Wang ₁ , Quan-Wei Wei ₇ , Peng-Cheng Lin ₈ , Yan Lin _{1,

2} , Wei Xu _{1,

2,

9} , Cong-Jian Xu ₁ , Yi-Yuan Yuan _{1,

2} , Shi-Min Zhao _{1,

2,

4,

8}

Affiliation

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, Fudan University, Shanghai 200438, 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.

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 morphologic 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 apoptotic 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.

中文翻译：

卵泡刺激激素控制颗粒细胞谷氨酰胺合成以调节排卵。

多囊卵巢综合征（PCOS）是无排卵性不孕的主要原因。对排卵驱动因素的了解不足阻碍了多囊卵巢综合症的干预。在此，我们报告促卵泡激素 (FSH) 控制卵泡液 (FF) 谷氨酰胺水平来确定排卵。小鼠排卵从暴露于 FF 的颗粒细胞 (GC) 凋亡开始。 FF 谷氨酰胺在排卵前的猪 FF 中降低，在 PCOS 患者中 FF 升高。高谷氨酰胺食物可提高 FF 谷氨酰胺抑制小鼠 GC 细胞凋亡并诱导激素、代谢和形态 PCOS 特征。从机制上讲，驱动卵泡发育的 FSH 促进 GC 谷氨酰胺合成，从而提高 FF 谷氨酰胺，从而通过灭活 ASK1-JNK 凋亡途径抑制 GC 凋亡来维持卵泡壁完整性。 FSH 和谷氨酰胺抑制培养的小鼠卵泡的破裂。在用谷氨酰胺或 EsR1-KO 诱导的 PCOS 模型中，谷氨酰胺去除或用二甲双胍或 AT-101 激活 ASK1-JNK 通路可逆转 PCOS 特征。这些表明谷氨酰胺、FSH 和 ASK1-JNK 通路可靶向缓解 PCOS。

更新日期：2024-07-01

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