高龄女性卵巢储备功能低下（DOR）是不孕症诊疗一大难题。研究证实DOR是卵巢内活性氧（ROS）与抗氧化剂失衡导致氧化应激损伤所致。国医大师夏桂成教授运用补肾促排卵汤治疗DOR，临床疗效显著。前期研究证实补肾促排卵汤可有效保护氧化应激损伤，氧化应激可通过FSH-FOXO1信号轴诱导颗粒细胞凋亡，表观遗传修饰调控抗氧化酶系统影响ROS清除。本项目借助小鼠DOR模型，运用RNA-seq，基因转染、RNAi等技术手段，研究补肾促排卵汤及有效成分在卵母细胞成熟过程中通过CFP1介导组蛋白H3K4甲基化调控抗氧化酶活性和通过FSH-FOXO1信号轴促进颗粒细胞存活，受精及早期胚胎发育过程中通过CRL4复合体激活TET酶介导DNA去甲基化激活基因表达，全面阐释补肾促排卵汤调控DOR小鼠氧化应激的作用机制，为补肾促排卵汤防治卵巢早衰、改善卵巢储备功能、提高卵子和胚胎质量提供科学依据。

Decline in ovarian reserve(DOR) in elderly women is a major problem in infertility diagnosis and treatment. Study confirms that DOR is induced by oxidative stress bacause of the imbalance of ROS and antioxidant in ovarian. Professor Xia Guicheng applied the Tonifying kidney and Inducing Ovulation Decoction for the treatment of Decline in ovarian reserve (DOR), the clinical effect was significant. Previous studies confirmed that Tonifying kidney and Inducing Ovulation Decoction can effectively protect oxidative stress injury. Oxidative stress can induce granulosa cell apoptosisby FSH-FOXO1 signal axis. Epigenetic modification can regulate the antioxidant enzyme systems to clear ROS. In this study, We used the mouse model of DOR to study the effect of Tonifying kidney and Inducing Ovulation Decoction and its active ingredients on the methylation mechanism of histone H3K4 to to regulate antioxidant enzyme activity by CFP1 and mechanism of granulosa cell survival in mice by FSH-PKA-PI3K-AKT-Foxo1 signal axis in the process of oocyte maturation. We also want to explore the mechanism of DNA demethylation to activate gene expression by TET enzyme mediated by CRL4 complex during fertilization and early embryonic development by means of RNA-seq, gene transfection, RNAi, et al. The purpose of the subject is to explore the mechanism of Tonifying kidney and Inducing Ovulation Decoction regulating oxidative stress in DOR mice and to provide experimental basis for the prevention and treatment of premature ovarian failure, improving ovarian reserve function, improving the quality of oocytes and embryos.