Effects of in utero exposure to bisphenol A on expression of RARalpha and RXRalpha mRNAs in murine embryos

J Reprod Dev. 2003 Dec;49(6):539-45. doi: 10.1262/jrd.49.539.

Abstract

Retinoic acid receptor (RAR) alpha and retinoid X receptor (RXR) alpha are key factors in a nuclear receptor-dependent signal. To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor (ED), on embryonic development, we examined the mRNA levels of RARalpha and RXRalpha in murine embryos, exposed in utero to BPA (2 microg/kg/day) at 6.5-17.5 days post-coitum (dpc), by the real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Higher levels of RARalpha mRNA in cerebra of male and female embryos of control groups were detected at 14.5 dpc. In utero BPA reduced the RARalpha mRNA expression. Higher levels of RXRalpha mRNA in cerebra of male and female embryos were seen at 12.5 dpc. The exposure decreased RXRalpha mRNA expression in male but not female embryos. No remarkable change in the RARalpha mRNA expression level was noted in cerebella of male or female embryos of the control group during embryonic development. Exposure to BPA increased expression levels of RARalpha mRNA in cerebella of male and female embryos at 12.5 dpc. Higher levels of RXRalpha mRNA in cerebella of male and female embryos were seen, but no remarkable changes were noted during embryonic development. BPA significantly decreased the expression levels of RXRalpha mRNA in cerebella of female embryos at 12.5, 14.5 and 18.5 dpc. RARalpha and RXRalpha mRNAs were expressed in gonads (testes and ovaries) of murine embryos from 12.5 to 18.5 dpc. In utero exposure to BPA decreased levels of RARalpha mRNA in testes of 14.5- and 18.5-dpc-embryos, levels of RXRalpha mRNA in testes of 14.5-dpc-embryos, and levels of RXRalpha mRNA in ovaries of 14.5-dpc-embryos. The present findings indicate that RARalpha and RXRalpha play crucial roles in organogenesis, and the growth and development of murine embryos, and will contribute to the assessment of the toxic effects of BPA on retinoid signals in embryogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Brain / metabolism
  • Cell Nucleus / metabolism
  • Embryo, Mammalian / metabolism*
  • Estrogens, Non-Steroidal / pharmacology
  • Female
  • Male
  • Maternal Exposure*
  • Mice
  • Mice, Inbred ICR
  • Phenols / pharmacology*
  • Pregnancy
  • Pregnancy, Animal
  • RNA, Messenger / metabolism*
  • Receptors, Retinoic Acid / biosynthesis*
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tissue Distribution
  • Transcription Factors / biosynthesis*

Substances

  • Benzhydryl Compounds
  • Estrogens, Non-Steroidal
  • Phenols
  • RNA, Messenger
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Transcription Factors
  • bisphenol A