雾霾天气PM2.5污染混合效应与早期妊娠失败的关系及分子机制研究

Ambient particulate matter (PM2.5) was associated with adverse birth outcomes, such as preterm delivery, low birth weight and birth defects. The effect of PM2.5 on early pregnancy loss and related mechanism was not clear. Our group had found that TSP and BaP were associated with embryo loss in early pregnancy. However, the components of PM2.5 are complicated which is various in different seasons and regions. The investigation of the relationship between mixed effect of PM2.5 and early pregnancy loss will be significant for controlling the exhausts of pollutants and reducing adverse pregnant outcomes. Epidemiology and molecular biological research will be used in our project in Tianjin where the air pollution is heavy. (1)Geographicical information system combined with advance GIS model and time-activity model will be performed for evaluating the outside exposure of PM2.5. The typical binding components will be screened to analyze pollution sources. Case-control study will be used to analyze the association between early pregnancy loss and maternal exposure of PM2.5 before pregnancy and during the first three months of pregnancy.(2)Exposure model of PM2.5 will be constructed based on SD rats. We attempt to explore the potential mechanism related to embryo nidation by the method of immunohistochemistry, PCR and Western-blot. All the researches are aimed to provide theory accordance for the prevention and reduction of adverse pregnant outcomes.

大气细颗粒物（PM2.5）污染可导致早产、低出生体重和出生缺陷等不良妊娠结局，其与早期妊娠失败的关系尚未明确。课题组前期发现大气总悬浮颗粒物（TSP）及PM2.5载带组分苯并芘与早期胚胎停育的发生有关。然而PM2.5成分复杂、季节地域差别大，因此分析PM2.5的混合效应与早期妊娠失败的关系，解析其来源，对控制污染源排放、减少不良妊娠的发生意义重大。本课题拟在污染较重的天津地区开展流行病学和分子生物学两个层面的研究:(1)利用地理信息系统，结合先进的GIS模型和时空活动模式评估PM2.5的外暴露水平，筛选载带的典型组分进行源分析；病例对照研究分析孕前与孕早期PM2.5的暴露与早期妊娠失败的关系；(2)构建SD大鼠PM2.5的暴露模型，利用免疫组化、PCR、蛋白印迹等分子生物学方法，从胚胎着床机制的角度探讨PM2.5致早期妊娠失败的可能机制，为今后的预防和干预提供理论依据。

大气细颗粒物（PM2.5）污染可导致早产、低出生体重和出生缺陷等不良妊娠结局，其与早期妊娠失败的关系尚未明确。我们研究发现PM2.5载带组分苯并(a)芘与早期妊娠失败的发生有关。PM2.5 表面载带的重金属 As 、Sb 是其主要毒性成分。PM2.5可能通过抑制滋养细胞增殖、损伤细胞DNA、改变细胞周期以及经线粒体凋亡途径引发细胞凋亡，干扰滋养细胞的正常生理功能。通过引起子宫基质金属蛋白酶MMPs/TIMPs 平衡紊乱而导致胚胎植入失败，从而影响妊娠。PM2.5可通过上调滋养细胞内MMPs抑制剂mRNA和蛋白的表达从而抑制细胞的迁移与侵袭能力，造成胎盘侵入子宫蜕膜过浅，子宫血管重塑障碍，增加早期妊娠失败的风险。本研究从胚胎着床机制的角度探讨了PM2.5致早期妊娠失败的可能机制，旨在为今后的预防和干预提供理论依据。