摘要：Highlights•MiR-17, miR-20a and miR-92a were inversely associated with prenatal PM2.5exposure.•Cluster activatorC-MYCwas inversely associated prenatal PM2.5exposure.•No association between the cluster targetCDKN1Aand gestational PM2.5exposure.AbstractBackgroundAir 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.ObjectivesHere, for the first time the potential prenatal effects of particulate matter with a diameter2.5) exposure on expression of the miR-17/92 cluster in cord blood are explored.MethodsIn 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 ofC-MYCandCDKN1A, 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 PM2.5exposure.ResultsPM2.5exposure averaged (10th-90thpercentile) 11.7 (9.0–14.4) µg/m3over the entire pregnancy. In cord blood, miR-17 and miR-20a showed a −45.0% (95%CI: −55.9 to −31.4,p ) and a –33.7% (95%CI: −46.9 to −17.2,p = 0.0003), decrease in expression in association withfirsttrimester PM2.5exposure, 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 PM2.5exposure during theentirepregnancy. In association withthirdtrimester PM2.5exposure, 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 PM2.5exposure during thelast monthof pregnancy.C-MYCexpression was downregulated in cord blood in association with prenatal PM2.5exposure during thefirsttrimester and theentirepregnancy, in the adjusted model.DiscussionLower expression levels of the miR-17/92 cluster in cord blood in association with increased prenatal PM2.5exposure were observed. Whether this oncogenic microRNA cluster plays a role intrans-placental carcinogenesis remains to be elucidated.
