Background

Air pollution exposure during pregnancy is an important environmental health issue. Epigenetics mediate the effects of prenatal exposure and could increase disease predisposition in later life. The oncogenic miR-17/92 cluster is involved in normal development and disease.

Objectives

Here, for the first time the potential prenatal effects of particulate matter with a diameter<2.5 μm (PM_2.5) exposure on expression of the miR-17/92 cluster in cord blood are explored.

Methods

In 370 mother-newborn pairs from the ENVIRONAGE birth cohort, expression of three members of the miR-17/92 cluster was measured in cord blood by qRT-PCR. Expression of C-MYC and CDKN1A, a cluster activator and a target gene, respectively, was also analyzed. Multivariable linear regression models were used to associate the relative m(i)RNA expression with prenatal PM_2.5 exposure.

Results

PM_2.5 exposure averaged (10^th-90^th percentile) 11.7 (9.0–14.4) µg/m³ over the entire pregnancy. In cord blood, miR-17 and miR-20a showed a −45.0% (95%CI: −55.9 to −31.4, p < 0.0001) and a –33.7% (95%CI: −46.9 to −17.2, p = 0.0003), decrease in expression in association with first trimester PM_2.5 exposure, and a –32.5% (95%CI: −45.6 to −16.3, p = 0.0004) and –23.3% (95%CI: −38.1 to −4.8, p = 0.02), respectively, decrease in expression in association with PM_2.5 exposure during the entire pregnancy. In association with third trimester PM_2.5 exposure, a reduction of −25.8% (95%CI: −40.2 to −8.0, p = 0.007) and −14.2% (95%CI: −27.7 to 1.9, p = 0.08), for miR-20a and miR-92a expression, respectively, was identified. Only miR-92a expression (-15.7%, 95%CI: −27.3 to −2.4, p = 0.02) was associated with PM_2.5 exposure during the last month of pregnancy. C-MYC expression was downregulated in cord blood in association with prenatal PM_2.5 exposure during the first trimester and the entire pregnancy, in the adjusted model.

Discussion

Lower expression levels of the miR-17/92 cluster in cord blood in association with increased prenatal PM_2.5 exposure were observed. Whether this oncogenic microRNA cluster plays a role in trans-placental carcinogenesis remains to be elucidated.

中文翻译：

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产前空气颗粒污染暴露和脐带血中 miR-17/92 簇的表达：来自 ENVIRONAGE 出生队列的结果。

背景

怀孕期间的空气污染暴露是一个重要的环境健康问题。表观遗传学介导产前暴露的影响，并可能增加晚年的疾病易感性。致癌的 miR-17/92 簇参与正常发育和疾病。

目标

在这里，首次探讨了暴露于直径<2.5 μm (PM _2.5 ) 的颗粒物对脐带血中 miR-17/92 簇表达的潜在产前影响。

方法

在来自 ENVIR ON AGE 出生队列的 370 对母婴中，通过 qRT-PCR 在脐带血中测量了三个 miR-17/92 簇成员的表达。还分别分析了C-MYC和CDKN1A、簇激活因子和靶基因的表达。多变量线性回归模型用于将相对 m(i)RNA 表达与产前 PM _2.5暴露相关联。

结果

在整个怀孕期间，PM _2.5的平均暴露量（第 10^个-90^个百分位数）为 11.7 (9.0–14.4) µg/m ^{3 。}在脐带血中，miR-17 和 miR-20a 显示为 -45.0%（95%CI：-55.9 至 -31.4，p < 0.0001）和 –33.7%（95%CI：-46.9 至 -17.2，p = 0.0003 ） ），与早孕期 PM _2.5暴露相关的表达减少，以及 –32.5%（95%CI：-45.6 至 -16.3，p = 0.0004）和 –23.3%（95%CI：-38.1 至 -4.8，p = 0.02 )，分别表示在整个怀孕期间与 PM _2.5暴露相关的表达减少。与对于 miR-20a，孕晚期PM _2.5暴露量减少 -25.8%（95%CI：-40.2 至 -8.0，p = 0.007）和 -14.2%（95%CI：-27.7 至 1.9，p = 0.08 ）分别鉴定了 miR-92a 和 miR-92a 的表达。只有 miR-92a 表达（-15.7%，95%CI：-27.3 到 -2.4，p = 0.02）与妊娠最后一个月的 PM _2.5暴露相关。在调整后的模型中，脐带血中的C-MYC表达下调与孕早期和整个妊娠期间产前 PM _2.5暴露相关。

讨论

观察到脐带血中 miR-17/92 簇的低表达水平与产前 PM _2.5暴露增加有关。这种致癌 microRNA 簇是否在跨胎盘癌发生中起作用仍有待阐明。