孕期细颗粒物暴露对新生儿早产风险的影响及胎盘外泌体介导的miRNA-21和miRNA-200a对其调控机制研究

早产的病因复杂。本人前期研究发现孕期细颗粒物（PM2.5）暴露与早产存在显著关联，但其生物学机制尚不清楚。有研究表明胎盘外泌体可以穿过胎盘屏障影响胎儿发育。我们的预实验也提示，胎盘外泌体miR-21和miR-200a的转录水平与PM2.5暴露和早产风险皆相关。因此我们提出“孕期PM2.5暴露—外泌体miR-21和miR-200a异常表达—早产”的假设。本项目拟从人群流行病学和体外细胞实验两个层面开展研究。拟在已有出生队列的基础上，基于活动轨迹模型评估PM2.5暴露，明确不同孕期PM2.5暴露与早产的暴露反应关系；并构建巢式病例对照研究，检测胎盘外泌体miR-21和miR-200a的转录水平，生物信息学技术预测靶基因，采用体外细胞实验对其生物学功能进行验证；综合分析miR-21和miR-200a在孕期PM2.5和早产关系中的调控机制。研究结果对阐明大气污染引起早产的生物学机制具有重要意义。

Preterm birth has a complex and multifactorial etiology. Our recent birth cohort study found that maternal exposure to fine particulate matter (PM2.5) was one important risk factor of preterm birth, however, the underlying biological mechanisms remained largely unknown. Previous studies have suggested that exosome released by mothers can pass through the placental barrier, and thus affect fetal development. Our pilot experimental study also observed that the exosome-mediated miRNA-21 and miRNA-200a in placenta were significant different between preterm births and term births. We therefore propose the hypothesis that maternal exposure to PM2.5 can affect the levels of exosomal miRNA-21 and miRNA-200a, which can increase the risk of preterm birth. To elucidate this hypothesis, this study will conduct both epidemiology and cellular experimental studies. Based on the existing birth cohort in Pearl River Delta, we will assess the personal exposure level of PM2.5 using an individual time activity model, collect the information on potential confounding factors, and follow up the women till the delivery of the babies; and then quantify the exposure-response relationship between PM2.5 exposure and preterm birth. At the same time, we will establish a nested case-control study, and detect the levels of exosomal miRNA-21 and miRNA-200a in placenta, predict their target genes using bioinformatics approach; and then examine their biological functions in vitro cell experiments. All these results will help to identify the potential mediating effects of exosomal miRNA-21 and miRNA-200a on the association between maternal PM2.5 exposure and preterm birth, and will enhance our understanding the biological mechanism of preterm birth caused by maternal PM2.5 exposure.