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Epigenetic responses following maternal dietary exposure to physiologically relevant levels of bisphenol A
Author(s) -
Anderson Olivia S.,
Nahar Muna S.,
Faulk Christopher,
Jones Tamara R.,
Liao Chunyang,
Kannan Kurunthachalam,
Weinhouse Caren,
Rozek Laura S.,
Dolinoy Dana C.
Publication year - 2012
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21692
Subject(s) - offspring , dna methylation , epigenetics , methylation , biology , benzhydryl compounds , endocrinology , medicine , gene , andrology , genetics , bisphenol a , gene expression , pregnancy , chemistry , organic chemistry , epoxy
Animal studies have linked perinatal bisphenol A (BPA) exposure to altered DNA methylation, but little attention is given to analyzing multiple physiologically relevant doses. Utilizing the viable yellow agouti ( A vy ) mouse, we examine the effects of developmental exposure through maternal diet to 50 ng BPA/kg ( n = 14 litters), 50 μg BPA/kg ( n = 9 litters), or 50 mg BPA/kg ( n = 13 litters) on global and candidate gene methylation at postnatal day 22. Global methylation analysis reveals hypermethylation in tail tissue of a/a and A vy /a offspring across all dose groups compared with controls ( n = 11 litters; P < 0.02). Analysis of coat color phenotype replicates previous work showing that the distribution of 50 mg BPA/kg A vy /a offspring shifts toward yellow ( P = 0.006) by decreasing DNA methylation in the retrotransposon upstream of the Agouti gene ( P = 0.03). Maternal exposure to 50 μg or 50 ng BPA/kg, however, results in altered coat color distributions in comparison with control ( P = 0.04 and 0.02), but no DNA methylation effects at the Agouti gene are noted. DNA methylation at the CDK5 activator‐binding protein ( Cabp IAP ) metastable epiallele shows hypermethylation in the 50 μg BPA/kg offspring, compared with controls ( P = 0.02). Comparison of exposed mouse liver BPA levels to human fetal liver BPA levels indicates that the three experimental exposures are physiologically relevant. Thus, perinatal BPA exposure affects offspring phenotype and epigenetic regulation across multiple doses, indicating the need to evaluate dose effects in human clinical and population studies. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.