Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A
Toxicol Lett
(2015)
232:293-300.
Abstract
Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0-3000mug/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000mug/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.
Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0-3000mug/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000mug/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.
MeSH terms
Age Factors Benzhydryl Compounds toxicity High Pressure Liquid Chromatography Computational Biology CpG Islands DNA Methylation drug effects Genetic Databases Energy Metabolism genetics Environmental Pollutants Liver Maternal Exposure Inbred C57BL Mice Phenols Phenotype Polymerase Chain Reaction Pregnancy Prenatal Exposure Delayed Effects Sex Factors Bisphenol A DNA methylation DREAM assay Developmental programming Epigenetics Female Gestational Age Bisulfite pyrosequencing metabolism
Age Factors Benzhydryl Compounds toxicity High Pressure Liquid Chromatography Computational Biology CpG Islands DNA Methylation drug effects Genetic Databases Energy Metabolism genetics Environmental Pollutants Liver Maternal Exposure Inbred C57BL Mice Phenols Phenotype Polymerase Chain Reaction Pregnancy Prenatal Exposure Delayed Effects Sex Factors Bisphenol A DNA methylation DREAM assay Developmental programming Epigenetics Female Gestational Age Bisulfite pyrosequencing metabolism
Note
Publication Date: 2015-01-05.
Publication Date: 2015-01-05.