Effects of in utero exposure to bisphenol A on mRNA expression of arylhydrocarbon and retinoid receptors in murine embryos.
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) alpha and retinoid X receptor (RXR) alpha, key factors in nuclear receptor-dependent retinoid 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 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 microg/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 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 RARalpha and RXRalpha 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 RARalpha 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 RXRalpha 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, RARalpha, and RXRalpha 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.
Nishizawa
Hanako
H
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University, Japan.
Morita
Maki
M
Sugimoto
Miki
M
Imanishi
Satoshi
S
Manabe
Noboru
N
D000818:Animals; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010053:Ovary / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D010968:Plasticizers; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; C000607072:Rara protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds