Environment International (Sep 2020)
Prenatal particulate air pollution exposure and expression of the miR-17/92 cluster in cord blood: Findings from the ENVIRONAGE birth cohort
Abstract
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 (PM2.5) 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 PM2.5 exposure. Results: PM2.5 exposure averaged (10th-90th 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 PM2.5 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 PM2.5 exposure during the entire pregnancy. In association with third trimester PM2.5 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 PM2.5 exposure during the last month of pregnancy. C-MYC expression was downregulated in cord blood in association with prenatal PM2.5 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 PM2.5 exposure were observed. Whether this oncogenic microRNA cluster plays a role in trans-placental carcinogenesis remains to be elucidated.
