Background: Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.
Objectives: We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.
Methods: The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants.
Results: We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants’ placentas. Methylation at these loci was moderately correlated (correlation coefficients range, –0.33 to –0.45) with EMID2 expression.
Conclusions:EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes.
1Penn State Tobacco Center of Regulatory Science, Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA; 2Department of Biostatistics, University of Kansas Medical Center, The University of Kansas, Kansas City, Kansas, USA; 3Center for the Study of Children at Risk, 4Department of Psychiatry and Human Behavior, and 5Department of Pediatrics, The Warren Alpert Medical School of Brown University and Women and Infants Hospital, Providence, Rhode Island, USA; 6College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon, USA; 7Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA; 8Department of Pathology and Laboratory Medicine, and; 9Department of Epidemiology, Brown University, Providence, Rhode Island, USA; 10Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
Recommended Citation:
Jennifer Z.J. Maccani,1 Devin C. Koestler,2 Barry Lester,et al. Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes[J]. Environmental Health Perspectives,2015-01-01,Volume 123(Issue 7):723