title: Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS).
abstract: The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.
authors.affiliation: a Departments of Preventive Medicine, Pediatrics, Oncological Science, Obstetrics , Gynecology and Reproductive Sciences; Icahn School of Medicine at Mount Sinai ; New York , NY USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Maya A
authors.initials: MA
authors.lastname: Kappil
authors.forename: An
authors.initials: A
authors.lastname: Li
authors.forename: Priyanthi S
authors.initials: PS
authors.lastname: Dassanayake
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Darrah
authors.forename: Alan E
authors.initials: AE
authors.lastname: Friedman
authors.forename: Michelle
authors.initials: M
authors.lastname: Friedman
authors.forename: Luca
authors.initials: L
authors.lastname: Lambertini
authors.forename: Philip
authors.initials: P
authors.lastname: Landrigan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stodgell
authors.forename: Yulin
authors.initials: Y
authors.lastname: Xia
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Nanes
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Aagaard
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Jeff C
authors.initials: JC
authors.lastname: Murray
authors.forename: Edward B
authors.initials: EB
authors.lastname: Clark
authors.forename: Nancy
authors.initials: N
authors.lastname: Dole
authors.forename: Jennifer
authors.initials: J
authors.lastname: Culhane
authors.forename: James
authors.initials: J
authors.lastname: Swanson
authors.forename: Michael
authors.initials: M
authors.lastname: Varner
authors.forename: Jack
authors.initials: J
authors.lastname: Moye
authors.forename: Carol
authors.initials: C
authors.lastname: Kasten
authors.forename: Richard K
authors.initials: RK
authors.lastname: Miller
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
mesh_terms: D001151:Arsenic / Q000032:analysis; D001559:Benzhydryl Compounds / Q000032:analysis; D002104:Cadmium / Q000032:analysis; D003632:Dichlorodiphenyldichloroethane / Q000032:analysis; D004785:Environmental Pollutants / Q000009:adverse effects / Q000032:analysis*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D056726:Genetic Association Studies; D055768:Halogenated Diphenyl Ethers / Q000032:analysis; D006801:Humans; D007854:Lead / Q000032:analysis; D008297:Male; D008628:Mercury / Q000032:analysis; D035683:MicroRNAs / Q000235:genetics*; D010636:Phenols / Q000032:analysis; D010920:Placenta / Q000737:chemistry* / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000032:analysis; D011247:Pregnancy; D000098826:Bisphenol A Compounds
chemical_list: D001151:Arsenic; D001559:Benzhydryl Compounds; D002104:Cadmium; D003632:Dichlorodiphenyldichloroethane; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D007854:Lead; D008628:Mercury; D035683:MicroRNAs; D010636:Phenols; D011078:Polychlorinated Biphenyls; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: birth cohort; environmental pollutants; epigenetics; microRNA; placenta