卵巢衰老卵母细胞质量下降是高龄女性生育力低下的主要因素，而卵巢衰老详细调控机制尚不明确。本课题前期研究发现衰老卵巢NAD+水平显著下降，进一步的实验发现NAD+合成通路不受影响，其主要消耗通路中sirtuin家族成员以及PARPs表达均显著下调，而CD38表达显著上调，提示NAD+含量的降低可能是CD38高表达过度消耗所致。NAD+是SIRT3的限速辅酶参与调控线粒体蛋白去乙酰化。基于前期实验结果我们提出假说：CD38表达上调导致卵巢NAD+含量降低，下调SIRT3蛋白活性，线粒体蛋白乙酰化水平升高，最终导致线粒体功能障碍诱发卵巢衰老及卵母细胞质量下降。为验证此假说，本研究拟采用构建基因敲除小鼠、Western Blot、RT-PCR、CO-IP、免疫荧光染色等技术阐明CD38高表达NAD+含量降低诱发线粒体功能障碍导致卵巢衰老的分子机制，为临床治疗提供新的实验和理论依据。

Ovary aging including the decline of oocyte quality is the main factor leading to the low fertility of aged women, however, the mechanism of ovary aging is still largely unknown. The previous results in the project found that the content of NAD+ in the aged ovary was decreased significantly than that of young controls. Further experiments showed that the expression of genes involved of NAD+ synthesis pathway was not affected, and the expression of genes in consumption pathway such as sirtuin family members and PARPs were significantly down-regulated, while the expression of CD38 was significantly up-regulated. Furthermore, the NAD+ is the limiting coenzyme of SIRT3 that is involved in regulating the acetylation of mitochondrial proteins. Based on all the results, we propose the following hypothesis: the upregulated CD38 is the major factor for the decreased NAD+ with ovary aging, which will lead to the dysfunction of mitochondria by effecting the activity of SIRT3, which results in the mitochondrial dysfunction and the lower quality of oocyte and reduced fertility. In order to test this hypothesis, the technologies such as constructing knockout mice, Western Blot, RT-PCR, CO-IP, immunofluorescence and so on was employed in this project to investigate the mechanisms of ovary aging, hoping for providing new experimental and theoretical basis for clinical treatment.