基于sox9/insulin信号途径探讨养精种玉汤合寿胎丸调节PCOS胎盘表观遗传效应的机制

研究认为胚胎时期宫内高雄环境引起胎儿在表观遗传水平重编程，最终导致出生后PCOS的发生。胎盘作为母体和胎儿联系的中介，介导胎儿的发育编程。然而，PCOS胎盘表观遗传效应尚不明确。课题组前期研究发现SOX9是PCOS胎盘低甲基化且表达上调的转录因子，过表达SOX9促进胎盘滋养层细胞分泌胰岛素。胰岛素过多将会引起胎儿怎样的表观遗传效应，值得深入探究。因此，我们提出以下科学假说：①SOX9促进胎盘滋养层细胞分泌胰岛素，高胰岛素环境引起胎儿发生表观遗传效应，最终引起PCOS的发生；②养精种玉汤合寿胎丸有效改善母系胎盘基因组表观遗传效应，减轻雌性子代的生殖和代谢异常。本课题拟以大鼠孕期高雄激素环境构建类人的PCOS妊娠模型，应用养精种玉汤合寿胎丸干预，采用MeDIP测序、CHIP技术等技术手段，旨在揭示胎盘SOX9调控胰岛素生成的功能，及探讨养精种玉汤合寿胎丸调节胎盘表观遗传效应的机制。

It has been suggested that intrauterine hyperandreogenism environment during fetal period causes reprogramming of fetal in the level of epigenetic, which ultimately leads to the occurrence of postnatal PCOS.The placenta acts as an intermediary between the mater and the fetus, mediating fetal developmental programming. However, the epigenetic of placenta in women with PCOS have not been studied. Our previous study found that PCOS placental sox9 is a transcription factor regulated by methylation, and overexpression of sox9 promoted the secretion of insulin in placental trophoblast cells. It is worth to investigate the effect of epigenetic caused by hyperinsulinemia. Therefore, we propose the following scientific hypotheses:① Placental SOX9 promotes insulin secretion, and hyperinsulinemia causes epigenetic effects on GnRH neurons in fetal hypothalamus, and finally leads to the occurrence of progeny PCOS;② Yangjing Zhongyu Tang and Shoutai Pill may effectively improve the epigenetic effect of the maternal placenta, alleviate the reproductive, metabolism and emotional abnormalities in female offspring. This study aim to explore the mechanism of the abnormal GnRH neurons in hypothalamus caused by the high expression of insulin in placenta SOX9. Moreover, to evaluate the effects of chinese compound formula Yangjingzhongyu and Shoutai Pill during pregnancy in PCOS-like rats model. Hence, the results of this study may be helpful to interpret the pathogenesis of PCOS from fetal epigenetic reprogramming.