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

Andrea Ulloa, Anda Gliga, Tanzy Love, Daniela Pineda, Daniel W Mruzek, Gene Watson, Philip Davidson, Conrad Shamlaye, J.J. Strain, Gary Myers, van Wijngaarden Edwin, Joelle Ruegg, Karin Broberg

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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 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.

Original languageEnglish
Article number106321
Pages (from-to)1-7
Number of pages7
JournalEnvironment International
Volume147
Early online date16 Dec 2020
DOIs
Publication statusPublished - 28 Feb 2021

Keywords

  • DNA methylation
  • Early life
  • Epigenetic
  • Fish consumption
  • MeHg
  • Methylmercury
  • Neurodevelopment

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