项目名称： 氧化应激状态下受精卵细胞周期停滞的Chk1/Cdc25分子机制

项目编号： No.81471522

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李志凌

作者单位： 汕头大学

项目金额： 73万元

中文摘要： 培养环境影响受精卵发育。前期研究发现：氧化应激性DNA损伤精子受精后受精卵分裂延迟，细胞周期检验点激酶Chk1、底物Cdc25激活；抗氧化剂EGCG促进DNA损伤精子受精后胚胎发育。由于精子DNA损伤依赖于受精后受精卵内修复，Chk1是检验点关键信号分子，Cdc25与细胞周期停滞关系密切。那么：受精卵受氧自由基损害的分裂延迟，是否与Chk1和Cdc25的激活有关? Cdc25如何介导细胞周期G2/M期停滞？我们设想：不良培养环境中受精卵分裂延迟可能涉及氧化应激状态下受精卵细胞周期停滞，且Chk1/Cdc25参与了G2/M期调控，对受精卵细胞个体纠错具有生物学意义。本课题拟在已建立的小鼠受精卵培养体系中，采用多种干预措施及检测手段，研究Chk1/Cdc25调控的氧化应激状态下受精卵细胞周期停滞的分子机制；探讨抗氧化剂对受精卵保护机制。完善受精卵损伤修复理论，为优化人类ART技术提供理论依据。

中文关键词： 氧化应激；受精卵；细胞周期；Chk1；Cdc25

英文摘要： The development of zygotes can be affected by culture environment, while the mechanism remains unknown. In our previous studies, we found that zygotes fertilized with oxidative stress-inducing DNA-damaged sperm showed mitotic delay with Chk1 and Cdc25 activation. Antioxidant epigallocatechin-3-gallate (EGCG) promoted the development of embryos fertilized with DNA-damage sperm. The repair of damaged sperm DNA relies on the proteins and mRNA stored in zygotes. Chk1 is the critical cell cycle checkpoint kinase and Cdc25 is closely associated with cell cycle arrest. Therefore, is it possible that the arrest of zygotes induced by oxygen radical is due to Chk1 and Cdc25 activation, and how does Cdc25 mediate G2/M arrest? We proposed that the mitotic delay of zygotes in adverse environment might be attributed to the cell cycle arrest mediated by Chk1/Cdc25 in zygotes under oxidative stress and this may have biological significance to error correction in individual zygote. Based on the mouse zygote cultivation system which our group has set up, we use a variety of interventions and testing means to investigate the cell cycle G2/M arrest in zygotes which is modulated by Chk1/Cdc25 under oxidative stress, to explore the protective mechanism of antioxidants for zygotes, to perfect the theory of zygote damage repair, and finally, to provide a theoretical basis to optimize human ART.

英文关键词： oxidative stress;zygote;cell cycle;Chk1;Cdc25