PARENT SESSION
TOXICOLOGY

Monday, August 2, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(93) EFFECTS OF IN UTERO EXPOSURE TO BISPHENOL A ON mRNA EXPRESSION OF ARYLHYDROCARBON AND RETINOID RECEPTORS IN MURINE EMBRYOS.

Nishizawa, Hanako¹, Imanishi, Satoshi¹, Sugimoto, Miki¹, Manabe, Noboru¹, ¹ Unit of Anatomy and Cell Biology, Kyoto, Japan

ABSTRACT- To evaluate the effects of low-dose exposure 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 retinoic acid receptor (RAR)alpha and retinoid X receptor (RXR)alpha, key factors in a nuclear receptor-dependent retinoids signal transduction, in murine embryos exposed in utero to BPA (0.02, 2, 200 and 20,000 microg/kg/day) at 6.5-13.5 or -17.5 days post coitum (dpc), using quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Extremely low-dose BPA (0.02 microg/kg/day; 1/100 the dose of environmental exposure) remarkably increased AhR mRNA expression in the cerebra, cerebella and gonads (both 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 microg/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 both RARa and RXRa mRNAs in the cerebra, cerebella and gonads of male and female 14.5- and 18.5-dpc-embryos. Extremely low-dose BPA (0.02 microg/kg/day) increased RARa mRNA expression levels in the cerebella of male and female 14.5- and 18.5-dpc-embryos and in gonads of female 14.5-dpc-embryos, and significantly increased RXRa mRNA expression levels 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 exposure of BPA up-regulates the mRNA expression of AhR, RARa and RXRa in murine embryos, indicating that BPA disrupts the receptor-dependent signal transducing systems. Our data will contribute to the assessment of the toxic effects of BPA on xenobiotic metabolism and retinoid signals in embryogenesis.

KEY WORDS: Bisphenol A (BPA), Arylhydrocarbon receptor (AhR), Murine embryo, Retinoid receptors