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2001 Fiscal Year Final Research Report Summary

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
KeywordsEndcrine disrupter chemicals / Sex determination / Sex differentiation / diethylstilbestrol / spermatogenesis / mouse / hypothalamus- hypophysis-gonadal axis
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

  • Research Products

    (14 results)

All Other

All Publications (14 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2003-09-17  

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