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

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.

• Publication year

  2015

• Venue

  Molecular and Cellular Endocrinology

• Publication date

  2015-12-05

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.mce.2015.09.028PMID 26427651
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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