title: Developmental exposure to bisphenol A alters expression and DNA methylation of Fkbp5, an important regulator of the stress response.
abstract: Bisphenol A (BPA), an abundant endocrine disruptor, affects stress-responsiveness and related behaviors in children. In rats, perinatal BPA exposure modifies stress response in pubertal offspring via unknown mechanisms. Here we examined possible epigenetic modifications in the glucocorticoid receptor gene and its regulator Fkbp5 in hypothalamus and hippocampus of exposed offspring. We found increased DNA methylation of Fkbp5 and reduced protein levels in the hippocampus of exposed male rats. Similar effects were obtained in a male hippocampal cell line when exposed to BPA during differentiation. The estrogen receptor (ER) antagonist ICI 182,780 or ERβ knock-down affected Fkbp5 expression and methylation similarly to BPA. Further, BPA's effect on Fkbp5 was abolished upon knock-down of ERβ, suggesting a role for this receptor in mediating BPA's effects on Fkbp5. These data demonstrate that developmental BPA exposure modifies Fkbp5 methylation and expression in male rats, which may be related to its impact on stress responsiveness.
authors.affiliation: School of Health Sciences, National and Kapodistrian University of Athens, Thivon 2str, Athens 11527, Greece. Electronic address: ekitraki@dent.uoa.gr.
authors.forename: Efthymia
authors.initials: E
authors.lastname: Kitraki
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden. Electronic address: ivan.nalvarte@ki.se.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nalvarte
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine (CMM) L8:00, 171 76 Stockholm, Sweden; Swedish Toxicology Science Research Center (Swetox), Forskargatan 20, 15136 Södertälje, Sweden. Electronic address: ali.alavian.ghavanini@swetox.se.
authors.forename: Ali
authors.initials: A
authors.lastname: Alavian-Ghavanini
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine (CMM) L8:00, 171 76 Stockholm, Sweden; Swedish Toxicology Science Research Center (Swetox), Forskargatan 20, 15136 Södertälje, Sweden. Electronic address: joelle.ruegg@swetox.se.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Rüegg
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D019261:Epithalamus / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010636:Phenols / Q000009:adverse effects*; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects*; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047629:Estrogen Receptor beta; D010636:Phenols; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; DNA methylation; Estrogen receptor beta; Fkbp5; HT22 cells; Hippocampus