Effects of Exposure <i>In Utero</i> to Bisphenol A on the Expression of Aryl Hydrocarbon Receptor, Related Factors, and Xenobiotic Metabolizing Enzymes in Murine Embryos

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  • NISHIZAWA Hanako
    Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • IMANISHI Satoshi
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • MANABE Noboru
    Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo

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  • 経胎盤的ビスフェノールA暴露がマウス胎仔におけるアリルヒドロカーボン受容体とその関連因子および生体異物代謝酵素の発現におよぼす影響
  • Effects of Exposure In Utero to Bisphenol A on the Expression of Aryl Hydrocarbon Receptor, Related Factors, and Xenobiotic Metabolizing Enzymes in Murine Embryos

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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 μg/kg/day) and 17β-estradiol (E2; 5 μg/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 μg/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.<br>

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