Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Maccani JZ

PROVIDER: S-EPMC4492267 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Maccani Jennifer Z J JZ Koestler Devin C DC Lester Barry B Houseman E Andrés EA Armstrong David A DA Kelsey Karl T KT Marsit Carmen J CJ

Environmental health perspectives 20150306 7

<h4>Background</h4>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.<h4>Objectives</h4>We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.<h4>Methods< ...[more]

PMID: 25748564

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Project description:BackgroundPrenatal cadmium (Cd) exposure has been implicated in both placental toxicity and adverse neurobehavioral outcomes. Placental microRNAs (miRNAs) may function to developmentally program adverse pregnancy and newborn health outcomes in response to gestational Cd exposure.MethodsIn a subset of the Rhode Island Child Health Study (RICHS, n = 115) and the New Hampshire Birth Cohort Study (NHBCS, = 281), we used small RNA sequencing and trace metal analysis to identify Cd-associated expression of placental miRNAs using negative binomial generalized linear models. We predicted mRNAs targeted by Cd-associated miRNAs and relate them to neurobehavioral outcomes at birth through the integration of transcriptomic data and summary scores from the NICU Network Neurobehavioral Scale (NNNS).ResultsPlacental Cd concentrations are significantly associated with the expression level of five placental miRNAs in NHBCS, with similar effect sizes in RICHS. These miRNA target genes overrepresented in nervous system development, and their expression is correlated with NNNS metrics suggestive of atypical neurobehavioral outcomes at birth.ConclusionsGestational Cd exposure is associated with the expression of placental miRNAs. Predicted targets of these miRNAs are involved in nervous system development and may also regulate placental physiology, allowing their dysregulation to modify developmental programming of early life health outcomes.ImpactThis research aims to address the poor understanding of the molecular mechanisms governing adverse pregnancy and newborn health outcomes in response to Gestational cadmium (Cd) exposure. Our results outline a robust relationship between Cd-associated placental microRNA expression and NICU Network Neurobehavioral Scales (NNNS) at birth indicative of atypical neurobehavior. This study utilized healthy mother-infant cohorts to describe the role of Cd-associated dysregulation of placental microRNAs as a potential mechanism by which adverse neurobehavioral outcomes are developmentally programmed.

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Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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