肥胖降低女性辅助生殖活产率，其脂肪组织分泌过量瘦素（leptin），血液及卵泡液中高leptin负面影响胚胎发育，机理尚不明确。我们前期研究发现女性体脂率与优质胚胎率呈负相关，高leptin模式动物囊胚率低且细胞数目少，单细胞转录组测序提示卵子AMPK- NRF1下游细胞呼吸链基因表达上调。据此提出假说：高leptin通过AMPK激活NRF1导致卵母细胞呼吸作用过度激活，产生过量自由基(ROS)，降低胚胎发育潜能。本研究拟：利用临床数据阐明leptin与体脂率的相关性，及与胚胎发育潜能的关联；采用卵母细胞体外成熟模型明确高leptin浓度对卵子及胚胎的影响，揭示其通过AMPK过度激活呼吸链产生过量ROS导致胚胎发育滞缓的分子机制；在高leptin小鼠模型体内进行机制验证及干预措施的探索。本项目有望为女性肥胖影响卵子及胚胎发育机制提供新认识，并为靶向治疗提供新途径。

Obesity reduces the live birth rate of female assisted reproduction, adipose tissue secretes excessive leptin, and high leptin in blood and follicular fluid negatively affects embryo development, but the mechanism is not clear. Our previous research found that female percentage of body fat was negatively correlated with high-quality embryo rate. High-leptin model animals had a low blastocyst rate and a small number of cells in blastocyts. Single-cell transcriptome of oocyte analysis suggested that the genes of respiratory chain was up-regulated , and this genes was regulated by AMPK-NRF1. According to this hypothesis, activation of NRF1 by high leptin through AMPK leads to excessive activation of oocyte respiration, production of excess free radicals (ROS), and reduced embryonic development potential. First, we will use clinical data to clarify the correlation between leptin and body fat rate, and their effect on embryonic development potential. Then oocyte in vitro maturation models were used to clarify the effects of high leptin concentrations on eggs and embryos. And reveals the mechanism that high leptin concentrations induced excessive ROS production by activating the respiratory chain through AMPK pathway. what is more we will validate the mechanism in vivo and exploration of intervention measures in high leptin mouse models. This project is expected to provide new insights into the mechanisms by which obese women affect oocyte and embryo development, and provide new approaches for targeted therapy.