烟酸促卵子发育提高受孕和治疗卵巢早衰的作用及机理研究

The abnormal follicles development can result in infertility or early manopause. Currently, the infertility rate is about 15% in general population, and many assisted reproductive centers adopt hormone to promote the follicle development for harvesting the oocytes. In premature ovarian failure treatment,doctors also take hormone replacement therapy as main treatment which can only achieve to relieve symptoms without completely cure,but increases the cancer risks of hormone-sensitive organs. To find a new way to promote the follicle development, we designed our project. Up to now, we have got the proteomics of different follicle development stages and some non-hormone ingredients which can promote follicle growth. Among those niacin could significantly improve the ovulation and release relevant manopause symptoms. Next step, our aim is to explore the molecular mechanism of niacin. Firstly,we will establish in vitro ovarian tissues culture system and the mouse model of ovarian function failure,then adopt molecular biology and cell biology techniques to in-depth understand the signal pathway of niacin regulating arrest, growth and apoptosis of oocytes and granular cells in vivo and in vitro, so that we could verify the value of niacin in curing the ovarian function decline. The project will illuminate the clinic treatment of niacin as a new non-hormomal drug for manopause disorders, infertility and premature ovarian failure.

卵泡发育异常是导致不孕不育、更年期提前甚至卵巢早衰的一个重要因素，而其临床治疗尚困难。目前有15%左右人群不孕,辅助生殖"试管婴儿"技术中主要使用激素促进卵泡发育以获得卵子。临床使用激素替代疗法改善卵巢早衰症状，却不能根本治疗，且有一定的致癌风险。因此我们前期针对卵子发育过程和卵泡成熟过程进行了蛋白表达差异分析和非激素类药物筛选，发现烟酸可以有效地促进卵泡发育。为了深入地了解烟酸对卵巢功能和卵泡成熟的调控及其分子机制，我们将建立体外卵巢组织培养体系和卵巢功能衰退小鼠模型，通过分子生物学、细胞生物学等技术从体外和体内两个途径深入研究烟酸对卵母细胞及颗粒细胞休眠、生长和凋亡信号通路的调控机制，探讨其促进卵泡发育治疗卵巢功能衰退的可行性。该项目将为开发烟酸作为非激素新药促进卵泡发育和治疗卵巢功能衰退导致的月经不调、不孕不育和卵巢早衰提供基础研究数据和治疗的新希望。

卵泡发育异常是导致不孕不育、更年期提前甚至卵巢早衰的一个重要因素，而其临床治疗尚困难。目前有15%左右人群不孕,辅助生殖“试管婴儿”技术中主要使用激素促进卵泡发育以获得卵子。临床使用激素替代疗法改善卵巢早衰症状，却不能根本治疗，且有一定的致癌风险。因此我们对卵泡成熟过程进行了蛋白表达差异分析和非激素类药物筛选，发现烟酸可以有效地促进卵泡发育。我们建立体外卵巢组织培养体系和卵巢功能衰退小鼠模型，通过分子生物学、细胞生物学等技术从体外和体内两个途径深入研究烟酸对卵母细胞及颗粒细胞休眠、生长和凋亡信号通路的调控机制，研究其促进卵泡发育治疗卵巢功能衰退的机理。我们发现烟酸可以促进休眠小卵泡的发育提升PCNA的表达量，同时通过减少凋亡来修复化疗和辐照导致的两种卵巢早衰模型。两种早衰模型的卵泡发育数目在治疗后得到增多。该项目将为开发烟酸作为非激素新药促进卵泡发育和治疗卵巢功能衰退导致的月经不调、不孕不育和卵巢早衰提供基础研究数据和治疗的新希望。