环境双酚A暴露导致精子质量下降及其DNA甲基化/羟甲基化异常的基础

项目名称： 环境双酚A暴露导致精子质量下降及其DNA甲基化/羟甲基化异常的基础

项目编号： No.81501318

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 苗茂华

作者单位： 上海市计划生育科学研究所

项目金额： 18万元

中文摘要： 近几十年来，男性精液质量出现明显的下降趋势，成为全球性的公共卫生问题。科学家们高度怀疑环境中有害物质特别是环境内分泌干扰物对男性精液质量的下降起到重要作用。双酚A(BPA)是环境内分泌干扰物的一种，在环境中分布广泛，动物实验中己明确其具有生殖毒性，申请者所在研究团队前期进行人群研究也证实其对男性生殖功能的影响，包括精液质量下降、激素水平改变、性功能下降等。但BPA对男性生殖的作用机制研究极其缺乏。申请人所在研究团队前期已建立了两个男性精子生物样本库，分别来自职业人群和一般人群。基于已有样本库申请者发现BPA能引起精子DNA LINE-1甲基化改变。本研究拟在已有样本库的基础上，建立BPA不同暴露水平的男性特征性精子DNA甲基化/羟甲基化差异谱，探讨不同暴露水平下BPA的表观遗传学效应，为全面揭示BPA暴露影响精子质量的分子机制奠定基础，有利于科学评价BPA的安全性，具有重要的公共卫生意义。

中文关键词： 精子质量；双酚A；DNA甲基化/羟甲基化谱；表观遗传学

英文摘要： In recent decades, a declining trend of men’s semen quality has been observed, which is becoming a global public health problem. Scientists highly suspect that harmful substances in the environment, especially environmental endocrine disruptors, may play an important role on the decreased semen quality. Bisphenol A is one of the environmental endocrine disrupting chemicals, which is widely distributed in the environment and its reproductive toxicity has been proved in animal studies. The population based studies conducted by applicant’s team found effects of BPA on men’s reproductive function, including the decrease in sexual function and semen quality, and altered hormone level. But studies on the mechanism behind BPA’s effects on male reproduction are scarce. The applicant’s team has established two bio-sample bank of male semen sample from occupational population and general population respectively, based on which, BPA exposure was found to be related to LINE-1 hypomethylation in spermatozoa. This study is to acquire the differential DNA methylation /hydroxymethylation profiling in spermatozoa, and explore the epigenetic effects related to different exposure levels of BPA based on the existing sperm samples. The present study aims to help for a comprehensive understanding of molecular mechanism behind BPA’s effects on sperm quality, and a better evaluation on the safety of BPA, which is of great public health significance.

英文关键词： semen quality;bisphenol A;DNA methylation/hydroxymethlation;epigenetics