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Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes

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https://ir.library.oregonstate.edu/concern/articles/gt54kp66c

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  • 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 highrisk 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.
  • This is the publisher’s final pdf. The published article is copyrighted by National Institute of Environmental Health Sciences and reproduced with permission from Environmental Health Perspectives The published article can be found at: http://ehp.niehs.nih.gov/. EHP has provided a 508-conformant table of contents summarizing the Supplemental Material for this article (see below) so that readers with disabilities may determine whether they wish to access the full, nonconformant Supplemental Material. If you need assistance accessing this or any other content on this site, please contact ehp508@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
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  • Maccani, J., Koestler, D. C., Lester, B., Houseman, E. A., Armstrong, D. A., Kelsey, K. T., & Marsit, C. J. (2015). Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes. Environmental Health Perspectives, 123(7), 723-729. doi:10.1289/ehp.1408561
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  • 123
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  • 7
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  • This research was funded by grants R01MH094609 from the National Institute of Mental Health/National Institutes of Health (NIH); R01ES022223, P01 ES022832, and T32ES007272 from the National Institute of Environmental Health Sciences/NIH; and RD83544201 from the U.S. Environmental Protection Agency. J.Z.J.M. received support from grant T32HL076134-04 from the National Heart, Lung, and Blood Institute for a postdoctoral fellowship at Brown University and the Miriam Hospital. J.Z.J.M. is now at the Penn State College of Medicine Tobacco Center of Regulatory Science (TCORS) and is funded by grant P50-DA-036107-01 from the NIH.
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