title: DNA methylation changes in the placenta are associated with fetal manganese exposure.
abstract: Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina's HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p=0.045). 713 loci were associated with Mn exposure (p<0.0001). Five significantly differentially-methylated (p<1.3×10(-7)) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44g. Our observations suggest a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation.
authors.affiliation: Penn State Tobacco Center of Regulatory Science (TCORS), College of Medicine, Department of Public Health Sciences, Hershey, PA, USA.
authors.forename: Jennifer Z J
authors.initials: JZ
authors.lastname: Maccani
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
authors.forename: E Andrés
authors.initials: EA
authors.lastname: Houseman
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Armstrong
authors.affiliation: Section of Biostatistics & Epidemiology, Department of Community and Family Medicine, Hanover, NH, USA; Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Electronic address: Carmen.J.Marsit@Dartmouth.edu.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA; Department of Epidemiology, Brown University, Providence, RI, USA.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D001724:Birth Weight; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008345:Manganese / Q000032:analysis*; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D009262:Nails / Q000737:chemistry*; D010920:Placenta; D011247:Pregnancy; D055815:Young Adult
chemical_list: D008345:Manganese
keywords: Epigenetics; In utero; LOC284276; Manganese; Methylation; Placenta; Pregnancy