排卵障碍是育龄期多囊卵巢综合征（PCOS）患者不孕的主要原因，研究PCOS患者排卵障碍的分子机制是生殖健康领域的重大需求。本课题组前期研究结果（已申请专利和发表文章）：EPHA7基因与C/EBPβ、KLF4和ADAMTS1等排卵关键基因存在调控关系，与PCOS排卵障碍密切相关。拟扩大临床样本量确认基因调控网络；拟对卵巢颗粒细胞或下丘脑神经元细胞条件性敲除Epha7小鼠，对去卵巢、GnRH抑制、类PCOS大鼠行外源性EPHA7注射等体内实验，研究排卵和生育力；拟对人和小鼠卵巢颗粒细胞、颗粒细胞系KGN、大鼠垂体和下丘脑神经元细胞行RNA-Seq、抑制或过表达、ChIP等体外实验，探索EPHA7在下丘脑、垂体和卵巢组织的表达差异，及EPHA7与排卵相关基因的互作机制，阐明EPHA7通过调节下丘脑-垂体-卵巢轴影响排卵和妊娠的机制。通过动物模型排卵的干预，为PCOS患者促排卵治疗提供理论基础。

Ovulation disorder is the main cause of infertility in reproductive women with polycystic ovary syndrome (PCOS). To study the molecular mechanism of ovulation disorder in PCOS patients is an important requirement in the field of reproductive health. In our previous research, we found the EPHA7 gene is closely related to ovulation disorder in PCOS, and it has regulatory relationships with C/EBPβ, KLF4, and ADAMTS1. We will further expand to collect more clinical samples to certify the interaction network of gene regulation. We will do some researches on mice models with ovarian or neuron in the hypothalamus -specific and conditional knockout of Epha7 gene , ovariectomized rat model, abarelix-treated (GnRH inhibition) rat model and PCOS-like rat model injected with recombinant EPHA7-Fc protein through the caudal veins, to observe the ability of ovulation-promotion and fertility. Molecular biological methods such as RNA-Seq, gene inhibition or over-expression, and ChIP of the in vitro experiments on human and mouse primary granulocyte cells, KGN cell line, rat primary pituitary cells and hypothalamus neuron cells will be conducted. EPHA7 gene expression in the hypothalamus, pituitary gland, and ovary tissues will be checked. These will help us to figure out molecular mechanisms of EPHA7 by regulating the role of the hypothalamus-pituitary-ovarian axis on ovulation and fertility of PCOS. We will intervene the ovulation of rats or mice models. These will provide the experimental and theoretical basis for the treatment of ovulation disorder in PCOS patients.