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

被引:40
作者
Huang, Madelyn C. [1 ]
Douillet, Christelle [2 ]
Dover, Ellen N. [1 ]
Styblo, Miroslav [1 ,2 ]
机构
[1] Univ N Carolina, Curriculum Toxicol, Sch Med, Chapel Hill, NC 27515 USA
[2] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, CB 7461, Chapel Hill, NC 27515 USA
关键词
Arsenic; Prenatal exposure; Diabetes; Vitamin; Folate; Methylcobalamin; Dietary supplementation; FOLIC-ACID; URINARY SPECIATION; SODIUM ARSENATE; DRINKING-WATER; PLASMA FOLATE; CORD BLOOD; IN-UTERO; METHYLATION; HOMOCYSTEINE; VITAMIN-B-12;
D O I
10.1007/s00204-018-2206-z
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 mu g 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.
引用
收藏
页码:1925 / 1937
页数:13
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