Air pollution-induced placental epigenetic alterations in early life: a candidate miRNA approach

Particulate matter (PM) exposure during in utero life may entail adverse health outcomes in later-life. Air pollution's adverse effects are known to alter gene expression profiles, which can be regulated by microRNAs (miRNAs). We investigate the potential influence of air pollution exposure in prenatal life on placental miRNA expression. Within the framework of the ENVIRONAGE birth cohort, we measured the expression of six candidate miRNAs in placental tissue from 210 mother-newborn pairs by qRT-PCR. Trimester-specific PM2.5 exposure levels were estimated for each mother's home address using a spatiotemporal model. Multiple regression models were used to study miRNA expression and in utero exposure to PM2.5 over various time windows during pregnancy. The placental expression of miR-21 (−33.7%, 95% CI: −53.2 to −6.2, P = 0.022), miR-146a (−30.9%, 95% CI: −48.0 to −8.1, P = 0.012) and miR-222 (−25.4%, 95% CI: −43.0 to −2.4, P = 0.034) was inversely associated with PM2.5 exposure during the 2nd trimester of pregnancy, while placental expression of miR-20a and miR-21 was positively associated with 1st trimester exposure. Tumor suppressor phosphatase and tensin homolog (PTEN) was identified as a common target of the miRNAs significantly associated with PM exposure. Placental PTEN expression was strongly and positively associated (+59.6% per 5 µg/m³ increment, 95% CI: 26.9 to 100.7, P 2.5 exposure. Further research is required to establish the role these early miRNA and mRNA expression changes might play in PM-induced health effects. We provide molecular evidence showing that in utero PM2.5 exposure affects miRNAs expression as well as its downstream target PTEN.

宫内生命阶段暴露于颗粒物（PM），可能会对个体晚年的健康造成不良影响。已知空气污染的不良效应可改变基因表达谱，而基因表达过程可受微小RNA（miRNAs）的调控。本研究旨在探讨产前空气污染暴露对胎盘miRNA表达的潜在影响。依托ENVIRONAGE出生队列的研究框架，我们通过实时定量荧光PCR（qRT-PCR）技术，检测了210对母婴胎盘组织中6个候选miRNA的表达水平。研究采用时空模型，基于每位母亲的家庭住址，估算其妊娠各阶段的PM2.5暴露水平。本研究采用多元回归模型，分析妊娠不同时间窗内的宫内PM2.5暴露与miRNA表达之间的关联。妊娠中期PM2.5暴露与miR-21（表达下调33.7%，95%置信区间：-53.2~-6.2，P=0.022）、miR-146a（下调30.9%，95%置信区间：-48.0~-8.1，P=0.012）及miR-222（下调25.4%，95%置信区间：-43.0~-2.4，P=0.034）的胎盘表达呈负相关；而妊娠早期PM2.5暴露与miR-20a及miR-21的胎盘表达呈正相关。研究发现，肿瘤抑制基因张力蛋白同源物（PTEN）是与PM暴露显著相关的miRNAs的共同靶基因。胎盘PTEN的表达与PM2.5暴露呈显著正相关（每升高5 µg/m³，表达上调59.6%，95%置信区间：26.9~100.7，P<0.001）。未来仍需开展进一步研究，以明确此类早期miRNA及mRNA表达变化在PM诱导的健康效应中所发挥的具体作用。本研究提供了分子层面的证据，表明宫内PM2.5暴露可影响miRNA的表达及其下游靶基因PTEN的表达。