Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Acta Obstet Gynecol Scand. 2020 Jan;99(1):119-126. doi: 10.1111/aogs.13719. Epub 2019 Oct 25.
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.
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.
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.
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.
多囊卵巢综合征是一种伴有慢性炎症的复杂内分泌疾病。前列腺素 E2（PGE2）是一种促炎因子，在多囊卵巢综合征患者的血清中表达增加。锌指基因 217（ZNF217）被认为是多囊卵巢综合征的候选基因。我们旨在研究 ZNF217 与多囊卵巢综合征中 PGE2 的关系。
我们使用脱氢表雄酮诱导的多囊卵巢综合征大鼠模型和多囊卵巢综合征妇女和非综合征妇女的人颗粒细胞来测量 ZNF217 和其他靶基因的表达。此外，我们还用人颗粒样肿瘤细胞 KGN 进行了体外实验以验证分子机制。
脱氢表雄酮处理的大鼠和多囊卵巢综合征妇女的颗粒细胞中 ZNF217 表达降低。前列腺素 E2 合成的关键酶环氧化酶 2 在大鼠和综合征妇女的颗粒细胞中高表达，卵泡液中 PGE2 浓度增加。此外，ZNF217 表达的降低被认为抑制了雌二醇的合成，这进一步促进了环氧化酶 2 和 PGE2 的合成。同时，PGE2 在 KGN 细胞中以剂量依赖的方式对 ZNF217 表达具有抑制作用。
多囊卵巢综合征妇女颗粒细胞中 ZNF217 的表达降低通过 PGE2 诱导炎症，而 PGE2 抑制 ZNF217 的表达以建立反馈环。这种机制可能解释了多囊卵巢综合征的发病机制。
