卵母细胞是雌性生殖的关键。线粒体作为卵母细胞中最丰富的细胞器，在生殖细胞的发育和质量以及胚胎发育等过程中发挥重要作用。同时，线粒体损伤在衰老等疾病引起雌性生殖减退中广泛报道。基于以往的研究缺乏线粒体功能障碍引起雌性生殖缺陷的直接实验证据。为此，我们借助mtDNA突变小鼠模型来探讨mtDNA突变对雌性生殖的影响和机制。初步实验证实，雌性mtDNA突变鼠生育力减退。基于mtDNA突变对其编码呼吸链蛋白功能的影响，我们推测，mtDNA突变影响其编码呼吸链蛋白的功能，引起能量不足和氧化应激，从而破坏了卵母细胞成熟和维持后续胚胎发育的潜能，并最终引起雌性过早不育。本研究将以mtDNA突变鼠（PolgAmut/mut）为模型，应用遗传学、分子生物学和细胞生物学等手段，拟对上述设想予以验证，以揭示线粒体DNA突变对雌性生殖的影响和机制，为改善线粒体功能障碍引起的生殖缺陷提供理论基础和分子靶标。

The oocyte is the major determinant of female reproduction. Mitochondrion, as the richest organelle in oocyte, plays an important role in the reproductive process, with influence on germ cell development and quality as well as embryonic development. Meanwhile，mitochondria damage have been widely reported in aging and metabolic diseases induced female fertility decline. While previous studies just suggested a link between mitochondrial function and female reproduction, it lacked direct, experimental evidence. We now address this question by using mtDNA mutaor mice, to investigate the causative link between mtDNA mutation and female reproduction, and the underlying mechanisms. Our preliminary results indicated a substantial loss of fertility in mtDNA mutator mice. Increased mtDNA mutation adversely affects the function integrity of electron transfer chain, which impairs ATP production and ROS balance. Therefore, we postulated mtDNA mutation induced energy deficiency and oxidative stress disrupted oocyte competence for maturation and subsequent early embryonic development, and ultimately led to premature infertility. Here by using mtDNA mutator mouse model, we will perform molecular, cellular and biochemical analysis to test the hypothesis above and uncover the molecular mechanism of mtDNA mutation in female reproduction, and to provide theoretical basis and molecular targets for improving reproductive defects caused by mitochondrial dysfunction.