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

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.

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。

大量研究已经评估了孕期大气细颗粒物（PM2.5）暴露和低出生体重的关系，但其与叶酸交互效应对低出生体重的影响尚不清楚，且PM1与低出生体重的关系研究极少。端粒功能异常是近年来学者们提出的大气污染健康危害效应的新机制，且另有证据表明PM2.5暴露和叶酸缺乏均可导致端粒功能异常。本项目基于端粒途径探讨孕期大气污染物和叶酸交互作用影响低出生体重的相关机制。我们在广东省茂名市前期建立的“环境污染物暴露对不良出生结局和儿童生长发育影响的出生队列”基础上，于2019年1月起随机选取孕早期入院的1601名孕妇作为研究对象，建立了出生队列，并跟踪至分娩结束。基于收集的脐带血，进行了端粒长度和端粒酶活性的检测。基于孕产妇孕期居住地址，采用“机器学习结合卫星遥感数据的反演方法”评估了孕早（1-13周）、中（14-26周）、晚期（27-40周）以及整个孕期（1-40周）的PM1、PM2.5、PM10、NO2和O3的暴露水平。研究发现，孕早期的空气污染物暴露浓度显著高于孕晚期的空气污染物暴露浓度。在孕早期时，PM2.5、PM10、PM1和NO2的暴露浓度每升高1个IQR时，新生儿出生体重分别显著降低40.94g、49.43g、41.93g和38.87g。以上结果表明大气颗粒物暴露可导致新生儿出生体重下降的暴露敏感期在孕早期。此外，基于孕妇孕期是否补充维生素或叶酸的亚组分析发现，在未补充维生素或叶酸孕妇中，大气污染物暴露与新生儿出生体重呈现负相关关系，而在补充维生素或叶酸孕妇中它们之间呈现显著的正相关关系，这表明孕期B族维生素的摄入对孕期大气颗粒物的健康危害效应可能具有缓解作用。并且，孕期大气污染物暴露会导致端粒功能紊乱，且这种影响会从孕早期一直持续到孕晚期。我们的研究结果为大气污染防控策略和干预措施的制定提供了理论依据。