title: Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.
abstract: The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez 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 µg/L (mean = 51.7 µg/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 µg/L (mean = 64.5 µg/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.
authors: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.
authors: Julia E
authors: JE
authors: Rager
authors: Kathryn A
authors: KA
authors: Bailey
authors: Lisa
authors: L
authors: Smeester
authors: Sloane K
authors: SK
authors: Miller
authors: Joel S
authors: JS
authors: Parker
authors: Jessica E
authors: JE
authors: Laine
authors: Zuzana
authors: Z
authors: Drobná
authors: Jenna
authors: J
authors: Currier
authors: Christelle
authors: C
authors: Douillet
authors: Andrew F
authors: AF
authors: Olshan
authors: Marisela
authors: M
authors: Rubio-Andrade
authors: Miroslav
authors: M
authors: Stýblo
authors: Gonzalo
authors: G
authors: García-Vargas
authors: Rebecca C
authors: RC
authors: Fry
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000328:Adult; D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D060766:Drinking Water / Q000737:chemistry; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D035683:MicroRNAs / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D015415:Biomarkers; D060766:Drinking Water; D035683:MicroRNAs; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: arsenic; epigenetics; gene expression; microRNAs; prenatal