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


OBJECTIVE
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.
Penn State Tobacco Center of Regulatory Science, Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA.
Jennifer Z J
JZ
Maccani
Devin C
DC
Koestler
Barry
B
Lester
E Andrés
EA
Houseman
David A
DA
Armstrong
Karl T
KT
Kelsey
Carmen J
CJ
Marsit
D002657:Child Development; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007223:Infant; D018730:Infant Behavior; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D008628:Mercury / Q000633:toxicity*; D009262:Nails / Q000737:chemistry*; D015997:Neonatal Screening; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000378:metabolism / Q000523:psychology; D012237:Rhode Island / Q000453:epidemiology
D008628:Mercury