Background: There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may affect disease propensity through epigenetic mechanisms.

Objective: The objective of this study was to determine whether prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and whether miRNA alterations are associated with birth outcomes.

Methods: Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR.

Results: For three miRNAs—miR-142-3p, miR15a-5p, and miR-185—we detected associations between Σphthalates or Σphenols on expression levels ( p < 0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden.

Conclusions: Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans.

Citation: LaRocca J, Binder AM, McElrath TF, Michels KB. 2016. First-trimester urine concentrations of phthalate metabolites and phenols and placenta miRNA expression in a cohort of U.S. women. Environ Health Perspect 124:380–387; http://dx.doi.org/10.1289/ehp.1408409

Address correspondence to K.B. Michels, Obstetrics and Gynecology Epidemiology Center, 221 Longwood Ave., Boston, MA USA. Telephone: (617) 732-4895. E-mail: kmichels@research.bwh.harvard.edu

We are indebted to A. Calafat and her team at the National Center for Environmental Health at the Centers for Disease Control and Prevention for biomarker measurements.

This project was supported in part by a pilot project grant from the Harvard–NIEHS (National Institute of Environmental Health Sciences) Center for Environmental Health (P30ES000002). J.L. was supported by the Harvard University Center for the Environment Fellowship. A.M.B. was supported by training grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health (NIH). T.F.M. was, in part, supported by R01ES018872 from the NIEHS/NIH. K.B.M. was supported by grant K01ES015771 from the NIEHS/NIH. The Epigenetic Birth Cohort was funded by research grant R21CA128382 from the National Cancer Institute, NIH.

The authors declare they have no actual or potential competing financial interests.

Received: 12 March 2014 Accepted: 16 June 2015 Advance Publication: 19 June 2015 Final Publication: 1 March 2016

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