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

•Epigenetic effects of methylmercury exposure early in life are largely unknown.•Prenatal mercury and DNA methylation were measured in children from the Seychelles.•Prenatal mercury was associated with higher nervous system-related gene methylation.•Early life exposure to methylmercury may alter epi...

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Published in:	Environment international 2021-02, Vol.147, p.106321, Article 106321
Main Authors:	Cediel Ulloa, Andrea, Gliga, Anda, Love, Tanzy M., Pineda, Daniela, Mruzek, Daniel W., Watson, Gene E., Davidson, Philip W., Shamlaye, Conrad F., Strain, J.J., Myers, Gary J., van Wijngaarden, Edwin, Ruegg, Joelle, Broberg, Karin
Format:	Article
Language:	eng
Subjects:	Adult Animals Arbetsmedicin och miljömedicin Child Child Development DNA Methylation Early life Environmental Health and Occupational Health Epigenetic Female Fish consumption Health Sciences Humans Hälsovetenskap Medical and Health Sciences Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper MeHg Methylmercury Methylmercury Compounds - toxicity Neurodevelopment Pregnancy Prenatal Exposure Delayed Effects Seychelles
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Summary:	•Epigenetic effects of methylmercury exposure early in life are largely unknown.•Prenatal mercury and DNA methylation were measured in children from the Seychelles.•Prenatal mercury was associated with higher nervous system-related gene methylation.•Early life exposure to methylmercury may alter epigenetic programming in children. 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. 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. 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. 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. 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.
ISSN:	0160-4120 1873-6750 1873-6750