基于端粒途径探讨孕期PM2.5/PM1暴露和叶酸交互作用对新生儿出生体重的影响及其作用机制

大量研究已评估了孕期PM2.5暴露和叶酸对新生儿出生体重的单独效应，但两者交互作用对出生体重的影响尚不清楚，且PM1与出生体重的关系还未见报道。大气污染物暴露和叶酸缺乏均可导致端粒功能异常，且可能存在共同的效应通路。因此，本项目拟在前期建立的出生队列基础上，从端粒途径探讨孕期PM2.5/PM1和叶酸交互作用影响出生体重的相关机制。选取1036名孕妇（早期）作为研究对象，跟踪至分娩结束，并记录新生儿出生体重等结局。分别于孕早、中、晚期采用空间统计模型评估母亲PM2.5和PM1个体暴露情况；通过红细胞叶酸检测和膳食问卷评估叶酸水平；收集脐带血和胎盘组织，检测端粒长度、端粒酶活性和含量、以及端粒酶逆转录酶mRNA表达水平等生物学效应指标。综合评价孕期PM2.5/PM1和叶酸交互作用对新生儿出生体重的影响，以及端粒功能可能的中介效应。研究将为制定大气污染防控措施和干预策略提供科学依据。

Numerous studies have examined the relationships of prenatal exposure to ambient fine particulate matter (PM2.5) and folate levels with birth weight in neonates independently; however, the interactive effects of PM2.5 with folate on birth weight were seldom investigated. In addition, no studies have investigated the association between PM1 and birth weight up to now. Furthermore, evidence has shown that both air pollution exposure and folate deficiency could cause telomere dysfunctions, and might share a common set of basic biological mechanisms in causing the telomere dysfunctions. Therefore, the aim of this project is to explore the mediating role of telomere function on the interactive effects of prenatal PM2.5/PM1 exposure and folate on birth weight. We will recruit 1036 pregnant women in the first trimester of pregnancy, and follow them until birth to collect antenatal care data and birth weight of neonates. A spatial statistical model will be applied to assess individual PM2.5 and PM1 exposure concentrations by gestational period (first, second and third trimester of pregnancy). Both erythrocyte folate determination and dietary questionnaire will be applied to assess folate levels of the pregnant women. We will also collect umbilical cord blood and placenta tissues for determining telomere length, telomerase activity and content, and telomerase reverse transcriptase mRNA expression levels. We propose to comprehensively 1) evaluate the interactive effects of prenatal PM2.5/PM1 exposure and folate levels on birth weight in neonates; and 2) explore whether telomere mediates the interactive effects of the PM2.5/PM1 and folate on birth weight. Findings from this study would provide theoretical evidence for developing strategies for air pollution control and its public health intervention.