Fractalkine/CX3CR1在PCOS患者卵巢中的表达及对雌、孕激素合成的作用研究

A critical feature of ovarian function is the differentiation of the ovulatory follicle into the corpus luteum, which produces steroid hormones (estradiol, progesterone) that are required for the initiation and the maintenance of pregnancy. Polycystic ovary syndrome (PCOS) is a common disease in women of reproductive age, companied with inadequate luteal function, low estradiol and progesterone levels, causing the embryo implantation failure or early miscarriage. Our previous study found that fractalkine and receptor CX3CR1 were expressed in human luteinized granulosa cells, and increased progesterone synthesis by upregulating expression of enzymes StAR, 3-βHSD, and CYP11A. So it can be inferred that fractalkine may be involved in the synthesis of sex hormones of luteinized granulosa cells. Therefore we intend to further study that expression of fractalkine/CX3CR1 in patients with PCOS, effect on estradiol and progesterone production in luteinized granulosa cells, and the ways in which sex hormone synthesis was influenced. The study may help to solve clinical problems of the PCOS patients with inadequate luteal function, such as infertility, early abortion, etc.

人卵巢的颗粒细胞在黄体生成素的作用下发生黄素化，产生性激素雌二醇、孕酮等，起重要的生理作用。多囊卵巢综合征（PCOS）是育龄期妇女常见病，常伴有黄体功能不足，雌二醇、孕酮水平低，致胚胎植入失败或早期流产。我们的前期研究发现fractalkine及受体CX3CR1表达于人的卵巢黄素化颗粒细胞，且通过上调性激素合成酶StAR，3-βHSD和CYP11A的表达，增加孕酮生成。由此推论fractalkine可能参与黄素化颗粒细胞性激素的合成。本课题拟在此基础上进一步研究fractalkine/ CX3CR1在PCOS患者卵巢组织的表达特点、如何影响PCOS患者卵巢颗粒细胞的雌孕激素生成，及通过何种途径影响性激素合成，以期为解决临床上PCOS患者黄体功能不足造成的不孕、早期流产等问题打下基础。

低孕酮与多囊卵巢综合征（PCOS）患者的黄体功能缺陷有关。研究调节孕酮生物合成的机制对于PCOS患者的早孕期维持非常重要。人类卵巢表达fractalkine，据报道fractalkine调节健康女性颗粒细胞的孕酮生成。在本课题中，我们旨在研究PCOS患者中fractalkine的作用。我们发现PCOS患者卵泡液和颗粒细胞中fractalkine水平下调，伴随着孕酮产生减少和类固醇合成急性调节蛋白（StAR）表达的下调。给予fractalkine翻转PCOS患者降低的孕酮和StAR的表达。机制研究揭示，这一现象与PCOS患者颗粒细胞中被抑制的ERK活性有关。我们的发现揭示了fractalkine调节PCOS患者卵泡颗粒细胞的类固醇生成。