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Effects of endocrine disruptors on developing brain, with special reference to gene expression.

Research Project

Project/Area Number 15390334
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

FUSHIKI Shinji  Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Professor, 医学研究科, 教授 (80150572)

Co-Investigator(Kenkyū-buntansha) ITOH Kyoko  Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Associate Professor, 医学研究科, 助教授 (80243301)
YAOI Takeshi  Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Research Associate, 医学研究科, 助手 (40311914)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥10,300,000 (Direct Cost: ¥10,300,000)
Keywordsendocrine disruptor / bisphenol A / brain development / gene expression / cDNA microarray / BrdU / protein disulfide isomerase / immunohistochemistry / Protein Disulfide Isomerase
Research Abstract

To investigate the effects of in utero exposure to bisphenol A(BPA) on developing brain, we have studied fetal mouse brains that were exposed to BPA during embryonic period with molecular biological as well as immunohistochemical methods. BPA was given so to pregnant ICR mice, from the beginning of gestation to embryonic day 12.5, 14.5, 16.5, 18.5, respectively. Fetal telencephalons were processed for global gene analysis with microarrays containing more than 30,000 mouse gene fragments. Pregnant mice that were treated as mentioned above were given 5-bromo-2'-deoxyuridine (BrdU, 12.5mg.kg) ip, at E12.5, 14.5, 16.5, and 18.5. Fetuses were obtained by caesarean section, 1h after BrdU injection or 2-3days after. The brains were fixed and embedded in wax, followed by immunohistochemical staining for BrdU as well as protein disulfide isomerase(PDI) and other cell-differentiation markers. cDNA microarray analyses revealed up-regulation (2-fold difference in BPA-treated mice was regarded as being significant) of approximately 2% of genes, which included developmentally regulated genes such as Numb, and Lnx family. PDI immunoreactivity was discernible in the cortical plate, subplate, intermediate zone of dorsal neocortex and CA of hippocampus, from E12.5 to 16.5. PDI immunoreactivity was prominent in the cortical plate as radial distribution. BrdU-positive cell density in telencephalic wall was increased in all zones of developing cortex, from E12.5 to 14.5, which suggests accelerated stem cell proliferation and premature neuronal migration by BPA. TUJ1-positive projecting fibers showed more prominent fasciculation in BPA-treated mice. Our observation indicates that exposure to BPA at early to mid-embryonic period affects brain development in mice.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (10 results)

All 2005 2004 2003

All Journal Article (10 results)

  • [Journal Article] Spatiotemporal patterns of expression of IGSF4 in developing nervous system.2005

    • Author(s)
      Ohta Y, Itoh K, Yaoi T, Tando A, Fukui K, Fushiki S
    • Journal Title

      Dev Brain Res (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spatiotemporal patterns of expression of IGSF4 in developing nervous system.2005

    • Author(s)
      Ohta Y, Itoh K, Yaoi T, Tando S, Fukui K, Fushiki S.
    • Journal Title

      Dev Brain Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spatiotemporal patterns of Musashi1 expression during inner ear development.2004

    • Author(s)
      Sakaguchi H, Yaoi T, Suzuki T, Okano H, Hisa Y, Fushiki S
    • Journal Title

      NeuroReport 15

      Pages: 997-1001

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spatiotemporal patterns of Musashi1 expression during inner ear development.2004

    • Author(s)
      Sakaguchi H, Yaoi T, Suzuki T, Okano H, Hisa Y, Fushiki S.
    • Journal Title

      NeuroReport. 15

      Pages: 997-1001

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in neuronal migration in neocortex of connexin43 null mutant mice.2003

    • Author(s)
      Fushiki S, Perez Velazquez JL, Zhang L, Bechberger JF, Carlen PL, Naus CC
    • Journal Title

      J Neuropathol Exp Neurol 62

      Pages: 304-314

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of heavy ion particles on the developing murine cerebellum, with special reference to cell death.2003

    • Author(s)
      Kinoshita C, Yaoi T, Nojima K, Fushiki S
    • Journal Title

      Acta Histochem Cytochem 36

      Pages: 145-151

    • NAID

      110003144266

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel marker for terminal Schwann cells, homocysteine-responsive ER-resident protein, as isolated by a single cell PCR-differential display.2003

    • Author(s)
      Oda R, Yaoi T, Okajima S, Kobashi H, Kubo T, Fushiki S
    • Journal Title

      Biochem Biophys Res Commun 308

      Pages: 872-877

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in neuronal migration in neocortex of connexin43 null mutant mice.2003

    • Author(s)
      Fushiki S, Perez Velazquez JL, Zhang L, Bechberger JF, Carlen PL, Naus CC.
    • Journal Title

      J Neuropathol Exp Neurol. 62

      Pages: 304-314

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effects of heavy ion particles on the developing murine cerebellum, with special reference to cell death.2003

    • Author(s)
      Kinoshita C, Yaoi T, Nojima K, Fushiki S.
    • Journal Title

      Acta Histochem Cytochem. 36

      Pages: 145-151

    • NAID

      110003144266

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel marker for terminal Schwann cells, homocysteine-responsive ER-resident protein, as isolated by a single cell PCR-differential display.2003

    • Author(s)
      Oda R, Yaoi T, Okajima S, Kobashi H, Kubo T, Fushiki S.
    • Journal Title

      Biochem Biophys Res Commun. 308

      Pages: 872-877

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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