从子宫内膜蜕膜化及胚胎早期发育重要相关基因表达的甲基化调控探索叶酸缺乏所致胚胎发育异常的分子机制

项目名称： 从子宫内膜蜕膜化及胚胎早期发育重要相关基因表达的甲基化调控探索叶酸缺乏所致胚胎发育异常的分子机制

项目编号： No.31271246

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 何俊琳

作者单位： 重庆医科大学

项目金额： 80万元

中文摘要： 叶酸缺乏是胚胎发育异常的多因素病因之一。课题组前期研究发现在叶酸缺乏的情况下，孕鼠胚胎能够正常着床，但妊娠结局不利。子宫内膜蜕膜化、胎盘正常形成以及胚胎早期自身正常发育是着床以后妊娠建立和维持的重要生理环节，胎盘形成中各基因DNA甲基化模式可受到母体叶酸水平的影响。子宫内膜蜕膜化进程以及胚胎早期自身的发育过程中相关基因DNA甲基化是否也会受到叶酸水平的影响，最终造成胚胎发育异常，目前尚不清楚，值得关注。本项目通过构建叶酸缺乏孕鼠模型，采用甲基化特异性寡核苷酸微阵列分析技术、甲基化特异性PCR和亚硫酸氢钠测序等一系列分子生物学技术对子宫内膜蜕膜化进程以及胚胎早期发育重要相关基因DNA甲基化及其表达进行系统深入研究，旨在阐明低叶酸水平可能通过DNA甲基化修饰调控子宫内膜蜕膜化进程以及胚胎早期发育重要相关基因的表达从而导致胚胎异常发育的分子机制，为出生缺陷的防治探寻新的线索。

中文关键词： 叶酸缺乏；蜕膜化；胚胎早期发育；DNA甲基化；出生缺陷

英文摘要： Folate deficiency has been reported for the association with many birth defects. But the molecular mechanisms involved in it remain poorly understood. Folate, one of the B vitamins, provides the one-carbon units required for nucleic acid biosynthesis and methylation. It plays a key role in epigenetic regulation of gene expression. Folate deficiency, either by insufficient nutritional intake or dysregulated metabolism, will result in an impaired DNA synthesis and repair, an abnormal genomic methylation of DNA and other molecules. Embryo implantation, uterine decidualization, placentation, and embryo development are all crucial for successful pregnancy. In our last National Natural Science Funds project(No.30973195), we previously found that folate, at the deficiency status, was not able to influence embryo implantation, and the methylation and expression of moleculars essential for uterine receptivity was not altered either. Successful implantation does not mean to successful pregnancy. As the results shown in the our previous research, the pregnant outcome in folate deficiency was unsuccessful . The birth rate of fetal was significantly decreased and the mortality rate of pregnant mouse was obviously increased at the status of folate deficiency. As we known, normal uterine decidualization, normal placentation,

英文关键词： folate deficiency；decidualization；embryo development；DNA methylation；birth defects