大气细颗粒物对男（雄）性生殖损害和不良妊娠结局的遗传与表遗传学效应及机制研究

环境污染对生殖健康的影响与医学防护是国内外关注的热点科学问题，作为主要环境污染的大气细颗粒物对生殖健康的影响也越来越受到关注，但大气细颗粒物暴露对生殖健康的损伤作用和机制还很不清楚。本项目选取细颗粒物污染较重的重庆地区，首先通过站点监测、个体监测和成分解析明确细颗粒物时空分布特征，建立有效的细颗粒物暴露评估模型。继而以参加国家孕优计划的男性为研究对象，通过定群研究阐明细颗粒物对精液质量的影响；以定群研究结合前瞻性父-子生殖队列，评价细颗粒物对男性生殖和妊娠结局的影响。进一步采用体内、外暴露组模型深入分析细颗粒物暴露对男（雄）性生殖系统、受孕及妊娠结局损伤效应，从遗传损伤与DNA修复、DNA甲基化和miRNA组等关键途径分析其分子机制，阐明主要信号通路、关键性应答基因及miRNA的主要作用和机理。为进一步阐明细颗粒物对男（雄）性生殖和相关妊娠结局的影响及遗传学和表观遗传学机制提供科学依据。

The effect of environmental pollution on reproductive health, especially the reproductive damage induced by air fine particulate matter (pm2.5) has raised worldwide concern, but the hazard risk and the mechanism are still far from clear. The present study is (1)To investigate the level and ingredient of pm2.5 in Chongqing, one of the highly polluted cities in China. Identify the spatio-temporal distribution characteristics and construct valid predictive model of individual exposure. (2) By panel study and paternal-offspring cohort study based on the adult males who attend the national pre-pregnancy examination project, the effect of pm2.5 on male reproductive health and male-related pregnancy outcome would be evaluated. (3) To explore the mechanism of the pm2.5-lead toxicity, genetic damage & DNA repair, methylation alteration as well as miRNA profile would be investigated with in-vivo and in-vitro models, so that the key genes and pathways as well as the role of miRNA could be identified. This study is expected to promote the understanding of the effect and genetic&epigenetic mechanism of pm2.5-lead male reproductive damage and unfavorable male-related pregnancy outcome.