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

Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ - Environ. Health Perspect. (2015)

Bottom Line: 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.Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression.

View Article: PubMed Central - PubMed

Affiliation: Penn State Tobacco Center of Regulatory Science, Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Heat map demonstrating Hg tertile differences > 0.125. Placental samples in columns; 339 loci in rows. Methylation β-values indicated by key at top left. Below figure, color bars indicate Hg tertiles (green, low tertile; yellow, medium; red, high), infant sex (blue, males; pink, females), maternal ethnicity (purple, Caucasian; green, non-Caucasian), maternal age tertiles (light gray, 23–29 years; dark gray, 30–33 years; black, 34–39 years), birth weight group [orange, LGA (≥ 90%); teal, appropriate-for-gestational-age (AGA); olive, SGA (≤ 10%)].
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f2: Heat map demonstrating Hg tertile differences > 0.125. Placental samples in columns; 339 loci in rows. Methylation β-values indicated by key at top left. Below figure, color bars indicate Hg tertiles (green, low tertile; yellow, medium; red, high), infant sex (blue, males; pink, females), maternal ethnicity (purple, Caucasian; green, non-Caucasian), maternal age tertiles (light gray, 23–29 years; dark gray, 30–33 years; black, 34–39 years), birth weight group [orange, LGA (≥ 90%); teal, appropriate-for-gestational-age (AGA); olive, SGA (≤ 10%)].

Mentions: Mean methylation β-values were calculated for each locus by Hg tertile. Placental methylation epigenome-wide was associated with Hg (omnibus p = 0.017). At 339 loci, methylation differed by > 0.125 between tertiles (Figure 2; see also Supplemental Material, Table S2); generally, samples clustered by Hg and sex, but not by maternal ethnicity, maternal age, or birthweight group. Mean β-values increased monotonically with increasing Hg tertiles for 79 loci, 34 loci had a monotonic decrease with increasing tertiles, and 226 loci had a non-monotonic relationship across tertiles.


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

Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ - Environ. Health Perspect. (2015)

Heat map demonstrating Hg tertile differences > 0.125. Placental samples in columns; 339 loci in rows. Methylation β-values indicated by key at top left. Below figure, color bars indicate Hg tertiles (green, low tertile; yellow, medium; red, high), infant sex (blue, males; pink, females), maternal ethnicity (purple, Caucasian; green, non-Caucasian), maternal age tertiles (light gray, 23–29 years; dark gray, 30–33 years; black, 34–39 years), birth weight group [orange, LGA (≥ 90%); teal, appropriate-for-gestational-age (AGA); olive, SGA (≤ 10%)].
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492267&req=5

f2: Heat map demonstrating Hg tertile differences > 0.125. Placental samples in columns; 339 loci in rows. Methylation β-values indicated by key at top left. Below figure, color bars indicate Hg tertiles (green, low tertile; yellow, medium; red, high), infant sex (blue, males; pink, females), maternal ethnicity (purple, Caucasian; green, non-Caucasian), maternal age tertiles (light gray, 23–29 years; dark gray, 30–33 years; black, 34–39 years), birth weight group [orange, LGA (≥ 90%); teal, appropriate-for-gestational-age (AGA); olive, SGA (≤ 10%)].
Mentions: Mean methylation β-values were calculated for each locus by Hg tertile. Placental methylation epigenome-wide was associated with Hg (omnibus p = 0.017). At 339 loci, methylation differed by > 0.125 between tertiles (Figure 2; see also Supplemental Material, Table S2); generally, samples clustered by Hg and sex, but not by maternal ethnicity, maternal age, or birthweight group. Mean β-values increased monotonically with increasing Hg tertiles for 79 loci, 34 loci had a monotonic decrease with increasing tertiles, and 226 loci had a non-monotonic relationship across tertiles.

Bottom Line: 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.Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression.

View Article: PubMed Central - PubMed

Affiliation: Penn State Tobacco Center of Regulatory Science, Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA.

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.

No MeSH data available.


Related in: MedlinePlus