経胎盤ビスフェノールA(BPA)暴露が器官形成期のマウス胎仔におけるarylhydrocarbon受容体(AhR)とレチノイン酸受容体mRNA発現におよぼす影響
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概要
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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 arylhydrocarbon receptor (AhR), which binds with many EDs and plays crucial roles in xenobiotic metabolism, and of the retinoic acid receptor (RAR) α and retinoid X receptor (RXR) α, key factors in nuclear receptor-dependent retinoid signal transduction, in murine embryos exposed in utero to BPA (0.02, 2, 200, and 20,000 μg/kg/day) at 6.5-13.5 or 6.5-17.5 days post coitum (dpc), using the real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Extremely low-dose BPA (0.02 μg/kg/day; 1/100 the dose of environmental exposure) remarkably increased AhR mRNA expression in the cerebra, cerebella, and gonads (testes and ovaries) of male and female 14.5- and 18.5-dpc-embryos. In utero exposure to BPA at 2, 200, and 20,000 μg/kg/day also increased levels of AhR mRNA. In gonads of 14.5-dpc-embryos, AhR mRNA levels were elevated and showed diphasic (U) dose-response curves following exposure to BPA, but inverted U dose-response curves were obtained for 18.5-dpc-embryos. Exposure to BPA increased expression levels of RARα and RXRα mRNAs in the cerebra, cerebella, and gonads of male and female 14.5- and 18.5-dpc-embryos. Extremely low-dose BPA (0.02 μg/kg/day) increased RARα mRNA expression in the cerebella of male and female 14.5- and 18.5-dpc-embryos and in the gonads of female 14.5-dpc-embryos, and significantly increased RXRα mRNA expression in the cerebra and cerebella of male and female 14.5-dpc-embryos. The present findings confirm that in utero exposure to an extremely low dose of BPA up-regulates the mRNA expression of AhR, RARα, and RXRα in murine embryos and disrupts the receptor-dependent signal transducing systems, and will contribute to the assessment of the toxic effects of BPA on xenobiotic metabolism and retinoid signals in embryogenesis.
- 日本繁殖生物学会の論文
著者
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MANABE Noboru
Research Unit of Animal Life Sciences, Animal Resource Science Centre, The University of Tokyo
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西澤 華子
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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森田 眞紀
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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杉本 美紀
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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IMANISHI Satoshi
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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SUGIMOTO Miki
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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MORITA Maki
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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Sugimoto Miki
Unit Of Anatomy And Cell Biology Department Of Animal Sciences Kyoto University
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NISHIZAWA Hanako
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
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Manabe Noboru
Research Center For Food Safety Graduate School Of Agricultural And Life Sciences The University Of
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