人类配子、早期胚胎印记基因DNA甲基化缺陷与辅助生殖技术结局相关性的研究

项目名称： 人类配子、早期胚胎印记基因DNA甲基化缺陷与辅助生殖技术结局相关性的研究

项目编号： No.81460237

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 施晓鋆

作者单位： 贵州医科大学

项目金额： 48万元

中文摘要： 多数研究认为辅助生殖技术与印记基因DNA甲基化缺陷相关，可能导致生长发育异常，但研究结论多根据动物实验推断，相关的人类研究较为局限。我们的前期研究建立了人类单个卵细胞、单个胚胎的DNA甲基化检测技术，初步探索了与辅助生殖技术相关的印记基因甲基化缺陷的现象。本项目拟以辅助生殖流程中获得的配子、早期胚胎、绒毛和出生子代为对象，采用结合重亚硫酸盐限制性酶分析（COBRA）、重亚硫酸盐测序（BSP）、焦磷酸测序（pyrosequencing）等技术跟踪检测多个印记基因DNA甲基化状态，同时收集相应的受精、胚胎发育、妊娠、自然流产等相关数据，通过综合统计比较，阐明辅助生殖技术操作流程中印记基因甲基化缺陷的发生和传递的总体风险，揭示印记基因甲基化缺陷与辅助生殖结局的相关性，为进一步评价人类辅助生殖技术的安全性提供更多的科学依据。

中文关键词： 辅助生殖技术；人早期胚胎；印记基因；DNA甲基化；结局

英文摘要： Many studies revealed that the assisted reproductive technology(ART) may be related to aberrant DNA methylation of imprinted genes, resulting in abnormal growth and development. However, the conclusions were mainly inferred from the hypothesis of animal studies,and related human studies are limited. Our previous studies established the technique to examine the DNA methylation in single oocyte and single embryo; primarily investigated the aberrant DNA methylation of imprinted genes during ART procedure. In this study, we plan to trace the human gametes, early embryos, villus and offsprings, use the combined bisulfite restrictionan alysis (COBRA), bisulfite sequencing PCR (BSP) and pyrosequencing to examine their DNA methylation status of multiple imprined loci. Meanwhile we collect the corresponding data regarding fertiliztion, embryo development, pregnancy and spontaneous abortion for comprehensive analysis .We try to explain the general risks of abnormal methylation occurrence and epigenetic inheritance linked to ART; reveal the relationship between methylation defects and ART outcomes, providing more evidence for evaluating ART safety.

英文关键词： assisted reproductive technology;human early embryos;imprinted genes;DNA methylation;outcomes