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Prenatal arsenic exposure and dietary folate and methylcobalamin supplementation alter the metabolic phenotype of C57BL/6J mice in a sex-specific manner

  • Inorganic Compounds
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Abstract

Inorganic arsenic (iAs) is an established environmental diabetogen. The link between iAs exposure and diabetes is supported by evidence from adult human cohorts and adult laboratory animals. The contribution of prenatal iAs exposure to the development of diabetes and underlying mechanisms are understudied. The role of factors that modulate iAs metabolism and toxicity in adults and their potential to influence diabetogenic effects of prenatal iAs exposure are also unclear. The goal of this study was to determine if prenatal exposure to iAs impairs glucose metabolism in mice and if maternal supplementation with folate and methylcobalamin (B12) can modify this outcome. C57BL/6J dams were exposed to iAs in drinking water (0, 100, and 1000 µg As/L) and fed a folate/B12 adequate or supplemented diet from before mating to birth of offspring. After birth, dams and offspring drank deionized water and were fed the folate/B12 adequate diet. The metabolic phenotype of offspring was assessed over the course of 14 weeks. Male offspring from iAs-exposed dams fed the folate/B12-adequate diet developed fasting hyperglycemia and insulin resistance. Maternal folate/B12 supplementation rescued this phenotype but had only marginal effects on iAs metabolism in dams. The diabetogenic effects of prenatal iAs exposure in male offspring were not associated with changes in global DNA methylation in the liver. Only minimal effects of prenatal iAs exposure or maternal supplementation were observed in female offspring. These results suggest that prenatal iAs exposure impairs glucose metabolism in a sex-specific manner and that maternal folate/B12 supplementation may improve the metabolic phenotype in offspring. Further studies are needed to identify the mechanisms underlying these effects.

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Acknowledgements

The authors would like to thank Dr. Zuzana Drobna (North Carolina State University, Raleigh, NC, USA) for her advice regarding prenatal folate and B12 supplementation. This work was funded by NIH 1R01ES022697 and R01 ES022697-03S1 Grants to M.S. and NIEHS F31ES027743 Grant to M.H. Additional support was provided by NIH Grant DK 056350 to the Nutrition Obesity Research Center at UNC.

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  1. Curriculum in Toxicology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Madelyn C. Huang, Ellen N. Dover & Miroslav Stýblo

  2. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, CB# 7461, Chapel Hill, NC, USA

    Christelle Douillet & Miroslav Stýblo

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  1. Madelyn C. Huang
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  2. Christelle Douillet
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Correspondence to Miroslav Stýblo.

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Huang, M.C., Douillet, C., Dover, E.N. et al. Prenatal arsenic exposure and dietary folate and methylcobalamin supplementation alter the metabolic phenotype of C57BL/6J mice in a sex-specific manner. Arch Toxicol 92, 1925–1937 (2018). https://doi.org/10.1007/s00204-018-2206-z

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