高龄颗粒细胞源性外泌体中lncRNA-KCNQ1OT1上调MAPK通路加重卵子线粒体损伤导致卵子衰老的机制研究

线粒体损伤是诱发卵子衰老的关键因素。本课题前期研究发现高龄女性颗粒细胞外泌体会加剧卵子线粒体损伤及其相关的卵子衰老。我们通过生物信息学分析发现lncRNA-KCNQ1OT1与多种卵子发育及衰老相关miRNA有关，并进一步证实高龄颗粒细胞源性外泌体中lncRNA-KCNQ1OT1的表达显著升高。但lncRNA-KCNQ1OT1对卵子线粒体损伤及其相关卵子衰老是否存在调控作用及其机制目前尚不明确。本课题将通过卵子线粒体损伤体内、体外模型研究高龄颗粒细胞源性外泌体中lncRNA-KCNQ1OT1对卵子线粒体损伤及卵子衰老的调控作用，并阐明lncRNA-KCNQ1OT1在MAPK信号通路中的作用靶点。本课题的实施将为卵子衰老的深入研究提供理论基础及新思路。

Mitochondrial damage is one of the most important factors inducing oocyte aging. In our previous work, oocyte cultured with exosomes from aged granulosa cells are more likely to have mitochondrial damage and to become aged. We did bioinformatics analysis and found that lncRNA-KCNQ1OT1 is related to several miRNAs regulating oocyte development and aging. We further confirmed that lncRNA-KCNQ1OT1 expresses significantly higher in exosomes of aged granulosa cells. It is still unclear whether lncRNA-KCNQ1OT1 has the effect of inducing mitochondrial damage and aging of oocyte. This study will focus on the impact of lncRNA-KCNQ1OT1 in exosomes of aged granulosa cells on mitochondrial damage and oocyte aging. Besides, we will further study the targets of lncRNA-KCNQ1OT1 in MAPK pathway. Our study will provide a new insight of oocyte aging.