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Prenatal methylmercury exposure and DNA methylation in seven-year-old children in the Seychelles Child Development Study

Cediel Ulloa, Andrea ; Gliga, Anda ; Love, Tanzy M ; Pineda, Daniela LU ; Mruzek, Daniel W ; Watson, Gene E ; Davidson, Philip W ; Shamlaye, Conrad F ; Strain, J J and Myers, Gary J , et al. (2021) In Environment International 147.
Abstract

BACKGROUND: Methylmercury (MeHg) is present in fish and is a neurotoxicant at sufficiently high levels. One potential mechanism of MeHg toxicity early in life is epigenetic dysregulation that may affect long-term neurodevelopment. Altered DNA methylation of nervous system-related genes has been associated with adult mental health outcomes.

OBJECTIVE: To assess associations between prenatal MeHg exposure and DNA methylation (at the cytosine of CG dinucleotides, CpGs) in three nervous system-related genes, encoding brain-derived neurotropic factor (BDNF), glutamate receptor subunit NR2B (GRIN2B), and the glucocorticoid receptor (NR3C1), in children who were exposed to MeHg in utero.

METHODS: We tested 406 seven-year-old... (More)

BACKGROUND: Methylmercury (MeHg) is present in fish and is a neurotoxicant at sufficiently high levels. One potential mechanism of MeHg toxicity early in life is epigenetic dysregulation that may affect long-term neurodevelopment. Altered DNA methylation of nervous system-related genes has been associated with adult mental health outcomes.

OBJECTIVE: To assess associations between prenatal MeHg exposure and DNA methylation (at the cytosine of CG dinucleotides, CpGs) in three nervous system-related genes, encoding brain-derived neurotropic factor (BDNF), glutamate receptor subunit NR2B (GRIN2B), and the glucocorticoid receptor (NR3C1), in children who were exposed to MeHg in utero.

METHODS: We tested 406 seven-year-old Seychellois children participating in the Seychelles Child Development Study (Nutrition Cohort 2), who were prenatally exposed to MeHg from maternal fish consumption. Total mercury in maternal hair (prenatal MeHg exposure measure) collected during pregnancy was measured using atomic absorption spectroscopy. Methylation in DNA from the children's saliva was measured by pyrosequencing. To assess associations between prenatal MeHg exposure and CpG methylation at seven years of age, we used multivariable linear regression models adjusted for covariates.

RESULTS: We identified associations with prenatal MeHg exposure for DNA methylation of one GRIN2B CpG and two NR3C1 CpGs out of 12 total CpG sites. Higher prenatal MeHg was associated with higher methylation for each CpG site. For example, NR3C1 CpG3 had an expected increase of 0.03-fold for each additional 1 ppm of prenatal MeHg (B = 0.030, 95% CI 0.001, 0.059; p = 0.047). Several CpG sites associated with MeHg are located in transcription factor binding sites and the observed methylation changes are predicted to lead to lower gene expression.

CONCLUSIONS: In a population of people who consume large amounts of fish, we showed that higher prenatal MeHg exposure was associated with differential DNA methylation at seven years of age at specific CpG sites that may influence neurodevelopment and mental health.

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publishing date
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Contribution to journal
publication status
published
subject
in
Environment International
volume
147
article number
106321
publisher
Elsevier
external identifiers
  • pmid:33340986
  • scopus:85097765408
ISSN
1873-6750
DOI
10.1016/j.envint.2020.106321
language
English
LU publication?
yes
additional info
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
id
20076377-674b-43d6-9580-729c0922b12b
date added to LUP
2020-12-21 21:35:22
date last changed
2024-06-27 04:12:25
@article{20076377-674b-43d6-9580-729c0922b12b,
  abstract     = {{<p>BACKGROUND: Methylmercury (MeHg) is present in fish and is a neurotoxicant at sufficiently high levels. One potential mechanism of MeHg toxicity early in life is epigenetic dysregulation that may affect long-term neurodevelopment. Altered DNA methylation of nervous system-related genes has been associated with adult mental health outcomes.</p><p>OBJECTIVE: To assess associations between prenatal MeHg exposure and DNA methylation (at the cytosine of CG dinucleotides, CpGs) in three nervous system-related genes, encoding brain-derived neurotropic factor (BDNF), glutamate receptor subunit NR2B (GRIN2B), and the glucocorticoid receptor (NR3C1), in children who were exposed to MeHg in utero.</p><p>METHODS: We tested 406 seven-year-old Seychellois children participating in the Seychelles Child Development Study (Nutrition Cohort 2), who were prenatally exposed to MeHg from maternal fish consumption. Total mercury in maternal hair (prenatal MeHg exposure measure) collected during pregnancy was measured using atomic absorption spectroscopy. Methylation in DNA from the children's saliva was measured by pyrosequencing. To assess associations between prenatal MeHg exposure and CpG methylation at seven years of age, we used multivariable linear regression models adjusted for covariates.</p><p>RESULTS: We identified associations with prenatal MeHg exposure for DNA methylation of one GRIN2B CpG and two NR3C1 CpGs out of 12 total CpG sites. Higher prenatal MeHg was associated with higher methylation for each CpG site. For example, NR3C1 CpG3 had an expected increase of 0.03-fold for each additional 1 ppm of prenatal MeHg (B = 0.030, 95% CI 0.001, 0.059; p = 0.047). Several CpG sites associated with MeHg are located in transcription factor binding sites and the observed methylation changes are predicted to lead to lower gene expression.</p><p>CONCLUSIONS: In a population of people who consume large amounts of fish, we showed that higher prenatal MeHg exposure was associated with differential DNA methylation at seven years of age at specific CpG sites that may influence neurodevelopment and mental health.</p>}},
  author       = {{Cediel Ulloa, Andrea and Gliga, Anda and Love, Tanzy M and Pineda, Daniela and Mruzek, Daniel W and Watson, Gene E and Davidson, Philip W and Shamlaye, Conrad F and Strain, J J and Myers, Gary J and van Wijngaarden, Edwin and Ruegg, Joelle and Broberg, Karin}},
  issn         = {{1873-6750}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Environment International}},
  title        = {{Prenatal methylmercury exposure and DNA methylation in seven-year-old children in the Seychelles Child Development Study}},
  url          = {{http://dx.doi.org/10.1016/j.envint.2020.106321}},
  doi          = {{10.1016/j.envint.2020.106321}},
  volume       = {{147}},
  year         = {{2021}},
}