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Effects of fetal and neonatal exposure of male mice to diethylstilbestrol as endocrine disrupter on the reproductive and neuroendocrine system

Research Project

Project/Area Number 12836014
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionKitasato University

Principal Investigator

HOSHI Nobuhiko  Kitasato Univ. School of Veterinary Medicine and Animal Sciences Associate Professor, 獣医畜産学部, 助教授 (10209223)

Co-Investigator(Kenkyū-buntansha) SUGAWARA Teruo  Hokkaido Univ. School of Medicine Assistant Professor, 医学部, 助手 (40250451)
HASHIMOTO Osamu  Kitasato Univ. School of Veterinary Medicine and Animal Sciences Lecturer, 獣医畜産学部, 講師 (90317058)
HASEGAWA Yoshihisa  Kitasato Univ. School of Veterinary Medicine and Animal Sciences Professor, 獣医畜産学部, 教授 (40092001)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsEndcrine disrupter chemicals / Sex determination / Sex differentiation / diethylstilbestrol / spermatogenesis / mouse / hypothalamus- hypophysis-gonadal axis / 内分泌撹乱化学物質 / 脳-下垂体-性腺系
Research Abstract

The purpose of this study is to determine the effect of fetal and neonatal exposure to diethylstilbestrol (DBS), as a representative endocrine disrupter, on the reproductive function of male mice. Various doses (0.001-100 μg) of DES or a vehicle (control) were administered to the neonatal group on day 3 (single) and on every 2 days from day 3 (N-long-term), and to the fetal group every 2 days from 7 dpc (F-long-term). Endocrinological and morphological changes were evaluated at 25 days of age (immediately before the onset of puberty), 4, 6, 8, and 12 weeks of age. We established a non-RI solid phase immunoassay method, which enables multiple microassay (LH, FSH, PRL, testosterone, inhibin) of the same sample with high sensitivity and specificity. In single administration of 10 and 100 μg of DES at 4 weeks, N-long-term administration at 1.0 μg for 25 days and 10 μg for 6 weeks, aid F-long-term administration at 10 μg for 6 weeks, testis weights were significantly reduced, and no spermat … More ogenesis and immature seminiferous tubules were observed. DES injections caused dose-dependent retardation of pituitary LH, FSH. Using the morphometric immunodetection method for incorporated thymidine analog BrdU, the high-dose groups (10 & 100 μg) showed a marked disruption of sperm production and significant suppression of cellular proliferation in testes. Immunohistochemical analysis in each group showed that immunoreactive neurons for GnRH were generally fewer in number and had thinner neurites in the high-dose groups Immunoreactivity of Era and StAR (steroidogenic acute regulatory protein) in testes was decreased. Thus our findings indicate that 1) single neonatal exposure of male mice to 10 μg of DES can advance the spermatogenesis at 6 weeks of age; 2) long-term exposure of these mice, particularly from fetus, could not recover the spermatogenesis even under 1.0 μg of DES; and 3) there is threshold dose of DES, and these delay and damage in the reproduction system due to reduction of pituitary gonadotropin production. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yamamoto R: "Lens culinaris agglutinin-reactive α-fetoprotein, an alternative variant to α-fetoprotein in prenatal screening for Down's syndrome"Hum Reprod. 16. 2438-2444 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T: "Molecular cloning and structural analysis of human sterol C5 desaturase"Biochim Biophys Acta. 1533. 277-284 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T: "The effect of the aryihydrocarbon receptor on the human steroidogenie acute regulatory gene promoter activity"Steroid Biochem Mol Biol. 78. 253-260 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T: "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1"Endocrinology. 142. 3570-3577 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T: "Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression"Endocrinology. 141. 2895-2903 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T: "PCR diagnosis of X-linked ichthyosis : identification of a novel mutation (E560P) of the steroid sulfatase gene"Hum Mutat. 15. 296 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hasegawa Y: "Cloned Animal and Placentation"Inhibins, activins and follistatins ; Novel regulators for the follicle development and oocvte growth. 6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto R et al.: "Lens culinaris agglutinin-reactive α-fetoprotein, an alternative variant to a-fetoprotein in prenatal screening for Down's syndrome"Hum Reprod. 16. 2438-2444 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T et al.: "Molecular cloning and structural analysis of human sterol C5 desaturase"Biochim Biophys Acta. 1533. 277-284 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T et al.: "The effect of the arylhydrocarbon receptor on the human steroidogenic acute regulatory gene promoter activity"Steroid Biochem Mol Biol. 78. 253-260 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T et al.: "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1"Endocrinology. 142. 3570-3577 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T et al.: "Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression"Endocrinology. 141. 2895-2903 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara T et al.: "PCR diagnosis of X-linked ichthyosis: identification of a novel mutation (E560P) of the steroid sulfatase gene"Hum Mutat. 15. 296 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hasegawa Y et al.: "Inhibins, activins and follistatins; Novel regulators for the follicle development and oocyte growth"Cloned Animal and Placentation. 3-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto R: "Lens culinaris agglutinin-reactive α-fetoprotein, an alternative variant to α-fetoprotein in prenatal screening for Down's syndrome"Hum Reprod. 16・11. 2438-2444 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara T: "Molecular cloning and structural analysis of human sterol C5 desaturase"Biochim Biophys Acta. 1533・3. 277-284 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara T: "The effect of the arylhydrocarbon receptor on the human steroidogenic acute regulatory gene promoter activity"Steroid Biochem Mol Biol. 78・3. 253-260 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara T: "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1"Endocrinology. 142・8. 3570-3577 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara,T.: "PCR diagnosis of X-linked ichthyosis : identification of a novel mutation (E560P) of the steroid sulfatase gene."Human Mutation. 15. 296 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kishida,T.: "Efficacy of maternal serum screening in the prenatal detection of fetal chromosome abnormalities in Japanese women."Fetal Diagn Ther.. 15. 112-117 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamada,H.: "A novel mutation (E113X) of anti-thrombin III gene (AT3) causing recurrent thrombosis in a woman with gestational recurrent thrombosis."Am.J.Hum.Genet.. 91. 348-350 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 星信彦: "産科婦人科学(II.性の分化・発育・成熟の異常.A.性の分化・発育・成熟の過程とその異常,B.性成熟の異常.)"加藤宏一,西谷巌ら編,ヘルス出版,東京. 636 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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