Developmental exposure to bisphenol A alters expression and DNA methylation of Fkbp5, an important regulator of the stress response

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:417

Article

Kitraki, Efthymia¹  Nalvarte, Ivan²  Alavian-Ghavanini, Ali^3,4  Rueegg, Joelle^3,4 

[1] Univ Athens, Sch Hlth Sci, Athens 11527, Greece

[2] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden

[3] Karolinska Inst, Ctr Mol Med CMM, Dept Clin Neurosci, S-17176 Stockholm, Sweden

[4] Swedish Toxicol Sci Res Ctr Swetox, S-15136 Sodertalje, Sweden

关键词: Bisphenol A;    DNA methylation;    Fkbp5;    Hippocampus;    HT22 cells;    Estrogen receptor beta;   

DOI  :  10.1016/j.mce.2015.09.028

来源: Elsevier

【 摘 要 】

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 ER beta knock-down affected Fkbp5 expression and methylation similarly to BPA. Further, BPA's effect on Fkbp5 was abolished upon knock-down of ER beta, 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. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

【 授权许可】

Free