Junyu Zhai1,2, Shang Li1,2, Xiaoyue Cheng1,2, Zi-Jiang Chen1,2,3, Weiping Li1,2, Yanzhi Du1,2. 1. Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China. 3. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, China.
Abstract
INTRODUCTION: Polycystic ovary syndrome is a complex endocrine condition with chronic inflammation. Prostaglandin E2 (PGE2) is a proinflammatory factor with an increased expression in the serum of women with polycystic ovary syndrome. Zinc finger gene 217 (ZNF217) is known as a candidate gene for polycystic ovary syndrome. We aimed to investigate the relation between ZNF217 and PGE2 in polycystic ovary syndrome. MATERIAL AND METHODS: We used a rat model of dehydroepiandrosterone-induced polycystic ovary syndrome and human granulosa cells both of women with polycystic ovary syndrome and of women without the syndrome to measure ZNF217 and other target gene expressions. In addition, we performed in vitro experiments with KGN human granulosa-like tumor cells to verify the molecular mechanisms. RESULTS: ZNF217 was decreased in the granulosa cells both of dehydroepiandrosterone-treated rats and of women with polycystic ovary syndrome. Cyclooxygenase 2, a key enzyme of PGE2 synthesis, was highly expressed in the granulosa cells of rats and women with the syndrome, and PGE2 concentration was increased in the follicular fluid. Furthermore, decreased ZNF217 expression was supposed to inhibit estradiol synthesis, which further promoted cyclooxygenase 2 and PGE2 synthesis. At the same time, PGE2 had an inhibitory effect on ZNF217 expression in a dose-dependent manner in KGN cells. CONCLUSIONS: Decreased ZNF217 expression in granulosa cells of women with polycystic ovary syndrome induced inflammation via PGE2, and PGE2 inhibited ZNF217 expression to establish a feedback loop. This mechanism might account for the pathogenesis of polycystic ovary syndrome.
INTRODUCTION:Polycystic ovary syndrome is a complex endocrine condition with chronic inflammation. Prostaglandin E2 (PGE2) is a proinflammatory factor with an increased expression in the serum of women with polycystic ovary syndrome. Zinc finger gene 217 (ZNF217) is known as a candidate gene for polycystic ovary syndrome. We aimed to investigate the relation between ZNF217 and PGE2 in polycystic ovary syndrome. MATERIAL AND METHODS: We used a rat model of dehydroepiandrosterone-induced polycystic ovary syndrome and human granulosa cells both of women with polycystic ovary syndrome and of women without the syndrome to measure ZNF217 and other target gene expressions. In addition, we performed in vitro experiments with KGN human granulosa-like tumor cells to verify the molecular mechanisms. RESULTS:ZNF217 was decreased in the granulosa cells both of dehydroepiandrosterone-treated rats and of women with polycystic ovary syndrome. Cyclooxygenase 2, a key enzyme of PGE2 synthesis, was highly expressed in the granulosa cells of rats and women with the syndrome, and PGE2 concentration was increased in the follicular fluid. Furthermore, decreased ZNF217 expression was supposed to inhibit estradiol synthesis, which further promoted cyclooxygenase 2 and PGE2 synthesis. At the same time, PGE2 had an inhibitory effect on ZNF217 expression in a dose-dependent manner in KGN cells. CONCLUSIONS: Decreased ZNF217 expression in granulosa cells of women with polycystic ovary syndrome induced inflammation via PGE2, and PGE2 inhibited ZNF217 expression to establish a feedback loop. This mechanism might account for the pathogenesis of polycystic ovary syndrome.
Authors: Jamaia S Waterbury; Maria E Teves; Alison Gaynor; Angela X Han; Grace Mavodza; Jordan Newell; Jerome F Strauss; Jan M McAllister Journal: J Endocr Soc Date: 2022-05-13