BMSCs调控ERRα/Mfn2/线粒体途径改善老龄化卵泡发育和质量的探索性研究

Improving follicle development and quality is very important for saving infertility induced by aged. Mitochondria are remarkably dynamic organelles, and play a very important role in the oocyte maturation and development. Mitofusin 2 is conserved, dynamin-like GTPase, which is essential for regulating mitochondrial fusion, energy metabolism and apoptosis. Our previous study showed that Mfn2 can affect oocytes development and quality by regulating mitochondria function. However, it is unknown that how to improve aged follicle quality by activating Mfn2 expression oocytes. In this study, we intend to use cell co-culture and gene transfection techniques to regulate Mfn2 expression in the mice prenatal follicle, and then, we observe the expressions of ERRα nd Mfn2 and oocytes development and quality. We hope this study could confirm that BMSCs regulate the follicle quality by activating ERRα and Mfn2 expressions and improving mitochondrial function, and provides valuable theoretical basis for the improvement of the clinical pregnancy rate of assisted reproductive technology, but also to seek for the protection for female fertility to a new study points.

改善卵子质量和维护卵泡正常发育是解决生殖衰老所致女性不孕的关键。线粒体在卵母细胞成熟和发育中发挥着非常重要的作用，线粒体融合蛋白Mfn2可以调节线粒体的融合、能量代谢及细胞凋亡。我们前期研究发现， Mfn2通过调节线粒体功能调控卵母细胞的发育及质量，然而，如何激活Mfn2表达并促使下游调控功能得于实现的关键机制尚不清楚。本课题在前期研究基础上深入探索卵泡发育的关键机制，我们拟用老龄小鼠的窦前卵泡为研究对象，利用骨髓间充质干细胞(BMSCs)－窦前卵泡共培养及基因转染技术，观察处理后老龄小鼠的窦前卵泡中ERRα、Mfn2的表达水平及窦前卵泡的成熟及质量。阐明BMSCs激活ERRα及Mfn2表达以调控线粒体功能，最终改善老龄化卵泡发育和质量的分子机制。本研究旨在揭示BMSCs作为改善老龄化卵泡发育和质量的“潜在能源”及其作用机制，为提高辅助生殖技术的成功率，保护女性生育功能提供新思路。

改善卵子质量和维护卵泡正常发育是解决生殖衰老所致女性不孕的关键。线粒体在卵母细.胞成熟和发育中发挥着非常重要的作用，线粒体融合蛋白Mfn2可以调节线粒体的融合、能量代.谢及细胞凋亡。我们前期研究发现， Mfn2通过调节线粒体功能调控卵母细胞的发育及质量，.然而，如何激活Mfn2表达并促使下游调控功能得于实现的关键机制尚不清楚。本课题在前期研.究基础上深入探索卵泡发育的关键机制，我们拟用老龄小鼠的窦前卵泡为研究对象，利用骨髓.间充质干细胞(BMSCs)－窦前卵泡共培养及基因转染技术，观察处理后老龄小鼠的窦前卵泡中E.RRα、Mfn2的表达水平及窦前卵泡的成熟及质量。阐明BMSCs激活ERRα及Mfn2表达以调控线粒.体功能，最终改善老龄化卵泡发育和质量的分子机制。本研究旨在揭示BMSCs作为改善老龄化.卵泡发育和质量的“潜在能源”及其作用机制，为提高辅助生殖技术的成功率，保护女性生育.功能提供新思路。