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Prenatal Arsenic Exposure and the Epigenome: Altered MicroRNAs Associated with Innate and Adaptive Immune Signaling in Newborn Cord Blood

Citation

Rager, Julia E.; Bailey, Kathryn A.; Smeester, Lisa; Miller, Sloane K.; Parker, Joel S.; Laine, Jessica E.; Drobna, Zuzana; Currier, Jenna M.; Douillet, Christelle; & Olshan, Andrew F., et al. (2014). Prenatal Arsenic Exposure and the Epigenome: Altered MicroRNAs Associated with Innate and Adaptive Immune Signaling in Newborn Cord Blood. Environmental and Molecular Mutagenesis, 55(3), 196-208. PMCID: PMC4023469

Abstract

The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 microg/L (mean = 51.7 microg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 microg/L (mean = 64.5 microg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations.

URL

http://dx.doi.org/10.1002/em.21842

Reference Type

Journal Article

Year Published

2014

Journal Title

Environmental and Molecular Mutagenesis

Author(s)

Rager, Julia E.
Bailey, Kathryn A.
Smeester, Lisa
Miller, Sloane K.
Parker, Joel S.
Laine, Jessica E.
Drobna, Zuzana
Currier, Jenna M.
Douillet, Christelle
Olshan, Andrew F.
Rubio-Andrade, Marisela
Styblo, Miroslav
Garcia-Vargas, Gonzalo G.
Fry, Rebecca C.

PMCID

PMC4023469