Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A

J C J van Esterik; A P Vitins; H M Hodemaekers; J H Kamstra; J Legler; J L A Pennings; W T Steegenga; C Lute; J Jelinek; J P J Issa; M E T Dollé; L T M van der Ven

doi:10.1016/j.toxlet.2014.10.021

Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A

Toxicol Lett. 2015 Jan 5;232(1):293-300. doi: 10.1016/j.toxlet.2014.10.021. Epub 2014 Oct 17.

Authors

J C J van Esterik¹, A P Vitins², H M Hodemaekers², J H Kamstra³, J Legler³, J L A Pennings², W T Steegenga⁴, C Lute⁴, J Jelinek⁵, J P J Issa⁵, M E T Dollé², L T M van der Ven⁶

Affiliations

¹ Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands; Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
² Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands.
³ Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
⁴ Division of Human Nutrition, Wageningen University, Bomenweg 2, Wageningen 6703 HD, The Netherlands.
⁵ Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA 19140, USA.
⁶ Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: leo.van.der.ven@rivm.nl.

PMID: 25455458
DOI: 10.1016/j.toxlet.2014.10.021

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 0-3000μg/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 3000μg/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.

Keywords: Bisphenol A; Bisulfite pyrosequencing; DNA methylation; DREAM assay; Developmental programming; Epigenetics.

MeSH terms

Age Factors
Animals
Benzhydryl Compounds / toxicity*
Chromatography, High Pressure Liquid
Computational Biology
CpG Islands
DNA Methylation / drug effects*
Databases, Genetic
Energy Metabolism / drug effects*
Energy Metabolism / genetics
Environmental Pollutants / toxicity*
Female
Gestational Age
Liver / drug effects*
Liver / metabolism
Maternal Exposure
Mice, Inbred C57BL
Phenols / toxicity*
Phenotype
Polymerase Chain Reaction
Pregnancy
Prenatal Exposure Delayed Effects
Sex Factors

Substances

Benzhydryl Compounds
Environmental Pollutants
Phenols
bisphenol A