Effects of exposure in utero to bisphenol a on the expression of aryl hydrocarbon receptor, related factors, and xenobiotic metabolizing enzymes in murine embryos

J Reprod Dev. 2005 Oct;51(5):593-605. doi: 10.1262/jrd.17026.

Abstract

To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor (ED), on embryonic development, we examined the mRNA expression levels of the aryl hydrocarbon receptor (AhR; which binds with many EDs and plays crucial roles in their metabolism) and related factors [aryl hydrocarbon receptor repressor (AhRR) and AhR nuclear translocator (Arnt)], xenobiotic metabolizing enzymes [XMEs; cytochrome P450 1A1 (CYP1A1) and UDP-glucuronosyltransferase, and the glutathione S-transferase Ya subunit (GST)], in murine embryos exposed in utero to BPA (0.02, 2, 200, and 20,000 microg/kg/day) and 17beta-estradiol (E2; 5 microg/kg/day, used as a positive control) at 6.5-13.5 or 6.5-17.5 days post coitum (dpc) using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Protein levels of CYP1A1 and GST in embryonic livers were estimated by Western immunoblotting. Exposure in utero to BPA [0.02 (1/100 dose of environmental exposure), 2, 200, and 20,000 microg/kg/day] increased AhR mRNA expression in the cerebra, cerebella, and gonads (testes and ovaries) of male and female mid-and late-developmental stage (14.5- and 18.5-dpc, respectively) embryos. BPA dose-independently up-regulated the expression of AhRR and Arnt in mid- and late-stage embryos. BPA had no remarkable effect on the mRNA levels of XMEs in mid-stage embryos, but dose-dependently up-regulated the expression in late-stage embryos. Moreover, the protein levels of these enzymes in the livers of late-stage embryos were increased. The present findings revealed that exposure to BPA in utero disrupts the expression of AhR and related factors and of xenobiotic metabolizing enzymes, and that mid-stage embryos, in the organogenic stage, are sensitive to BPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator / genetics
  • Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
  • Basic Helix-Loop-Helix Transcription Factors
  • Benzhydryl Compounds
  • Blotting, Western
  • Cerebellum / metabolism
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Embryonic Development / drug effects*
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Gonads / metabolism
  • Liver / metabolism
  • Male
  • Maternal Exposure / adverse effects*
  • Mice
  • Phenols / metabolism*
  • Phenols / toxicity
  • Pregnancy
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Aryl Hydrocarbon / biosynthesis*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telencephalon / metabolism

Substances

  • Ahrr protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Benzhydryl Compounds
  • Estrogens, Non-Steroidal
  • Phenols
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Repressor Proteins
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Cytochrome P-450 CYP1A1
  • Glutathione Transferase
  • bisphenol A