卵巢储备减退的线粒体/内质网氧化应激机制和临床助孕方案的研究

Diminished ovarian reserve (DOR) is happened in 30% of women who undergo assisted reproductive treatment, while about 60% of the women going to have their second child are over 35 years old. The etiology and pathophysiological progress in most of DOR women are still unknown, so their lowered fertility is very challenged in clinical reproductive medicine. Our previous studies indicated that disordered mitochondrial function, oxidative stress and increased aneuploidy rate are main pathomechanisms for DOR. We also found that some of antioxidant factors such as putrescine, endogenous PRDX4, and secretion of stem cells could balance the oxidative stress and improve the oocyte quality by the pathway of endoplasmic reticulum stress and calcium ions, and that IVF procedures with mini-stimulation protocol achieved a good outcome on DOR women. In this project, we will focus on three studies: (1) The main works included mitochondrial metabolism, dynamic Ca2+ and endoplasmic reticulum stress pathway, as the candidate makers for evaluation of ovarian function and IVF prognosis; (2) To explore the potential application of a group of new antioxidant factors for improving ovarian function, oocyte quality and embryonic developmental potential; (3) To optimize the mini- stimulation or natural cycle protocol of IVF for DOR women, to modify the pregnant outcome of individual-based assisted reproductive technologies.

卵巢储备减退（DOR）是一种卵巢退行性改变的状态，主要与高龄有关，包括病理性的原发性卵巢功能不全，占辅助生殖人群的30%。我国拟生育二孩的妇女中约60%超过35岁，其低生育力的助孕问题成为临床生殖医学的难点和热点。前期实验初步证实：DOR主要病理机制为卵母细胞线粒体功能低下、氧化应激和能量代谢系统损坏、染色体非整倍率增加；而一些抗氧化因子在人和动物的体内体外试验中，可在一定程度上修复氧化应激功能、改善卵母细胞质量；临床上辅助生殖技术的微刺激方案获得良好的助孕结果。本项目拟：①探索利用线粒体代谢、细胞内Ca2+、内质网应激等细胞事件相关的信号分子，评估卵母细胞质量和胚胎发育潜能。②研究PRDX4、腐胺、人间充质干细胞及分泌因子等物质改善DOR卵母细胞质量的机制和临床应用前景。③基于前期基础，研究个性化的卵巢微刺激助孕策略，提高DOR妇女活产率。