卵巢卵泡的发育和生长需要大量的物质供应和能量供应，特别是卵母细胞在成熟过程中伴随着大量颗粒细胞的增生，必然需要线粒体的适应性增加，否则将导致卵泡闭锁。在临床上也已经提示线粒体功能的改变与卵巢早衰有密切关系，提高线粒体功能有助于辅助怀孕。但是对于线粒体功能如何调控卵泡发育的机制目前还不清楚。在我们的前期工作中，建立了CRISP-Cas9技术在人颗粒细胞系中系统敲除基因的方法，成功筛选出了影响线粒体功能的HBP1新蛋白。并且通过建立Hbp1敲除小鼠，发现Hbp1对卵泡发育与储备起了关键作用。本项目将继续运用CRISP-Cas9方法筛选出新的影响线粒体功能的基因，并且深入研究Hbp1如何通过线粒体功能调控卵巢卵泡发育的细胞分子机制。通过筛选和功能分析相结合的方法，阐明线粒体对卵巢发育过程中的影响，为卵巢早衰以及辅助生育提供基础研究支撑。

Enhanced mitochondria adaption is considered to be critical for the ovary-follicular development and growth that demands a highly increased physical and energy supply, especially during the process of oocyte maturation which is accompanied by dramatic proliferation of granulosa cells. Otherwise, it will lead to follicular atresia. Clinically it has been suggested that mitochondrial function is closely related to premature ovarian failure while enhanced mitochondrial function will improve assisted reproduction. However, the genetic basis of mitochondrial function in the ovary development is poorly understood. Our previous work has established CRISP-Cas9-mediated targeting for genes conferring mitochondrial biogenesis in human GCT-derived KGN cells and found a novel gene, HBP1, in modulation of mitochondrial function. Preliminary analysis of ovary in Hbp1-/- mice revealed that Hbp1 deficiency resulted in increased number of follicle, suggesting the role of Hbp1 in follicle development. This project will continue to screen for the new gene in modulation of mitochondrial function by CRISP/Cas9 system, and to further study the molecular mechanisms of the regulation of mitochondrial adaption by Hbp1 which determines ovarian follicle development. Using screening and functional analysis, we will clarify the function of mitochondrial in ovarian development, and provide basic research support for premature ovarian failure and assisted reproduction technology.