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How reactive oxygen species mediate the effects of endocrine-disrupting agents on the reproductive organs?

Research Project

Project/Area Number 13671718
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOkayama University

Principal Investigator

SASAKI Junzo  Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Professor, 大学院・医歯学総合研究科, 教授 (30093686)

Co-Investigator(Kenkyū-buntansha) KOSAKA Jun  Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40243216)
YAMADA Teruo  Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Assistant, 大学院・医歯学総合研究科, 助手 (00033225)
NOMURA Takako  Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Assistant, 大学院・医歯学総合研究科, 助手 (20116437)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsendocrine-disrupting agents / DEHP / testis / rat / apoptosis / reactive oxygen species / DNA array / in situ hybridization / DNDアレイ / 内分泌撹乱物質 / cDNAマイクロアレイ
Research Abstract

In male reproductive organs, reactive oxygen species (ROS) such as hydrogen peroxide are known to be involved in sperm function. As di (2-ethylhexyl) phthalate (DEHP) (the plasticizers of synthetic polymers)-induced atrophy of the testis was inhibited by administration of ascorbic acid and vitamin E, the possible role of ROS has been suggested in the pathogenesis.
To test the possible involvement of oxidative stress in DEPH-induced atrophy, dynamic aspects of endogeneous antioxidants and gene expression in the rat testis were studied.
Degenerated primary spermatocytes and multinucleated spermatids appeared in the seminiferous tubules after 6-9 hrs of DEHP administration, and TUNEL-positive spermatocytes increased after 12 hrs of administration. DEHP increased the generation of ROS with a concomitant decrease in the concentration of glutathione and ascorbic acid in the testis. MEHP, metabolite of DEHP, induced the release of cytochrome c from isolated mitochondria of the testis. DNA array analysis revealed that DEHP treatment induced marked decrease of several genes, however, in situ hybridization histochemistry did not show localization patterns of gene products coincident with the gene profile. These results indicate that oxidative stress elicited by the administration of DEHP induced apoptosis in spermatocytes, thereby causing the atrophy of the testis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Ito, S et al.: "A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner"Biochem Biophys Res Commun. 280. 656-663 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori, H et al.: "Expression of phospholipid hydroperoxide glutathione peroxidase(PHGPx) mRNA in rat testis"Acta Histochem Cytochem. 34. 25-30 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kasahara, E et al.: "Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl) phthalate"Biochem J. 365. 849-856 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto, H et al.: "The expression of copper, zinc superoxide dismutase(Cu/Zn-SOD) in the rat submandibular gland"Biomed Res. 23. 85-90 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura, F et al.: "Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth"Am J Pathol. 161. 2047-2052 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hanada, H et al.: "Cyclosporin A inhibits thyroid hormone-induced shortening of the tadpole tail through membrane permeability transition mechanism"Comp Biochem Physiol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito S, Sakai A, Nomura T, Miki Y, Ouchida M, Sasaki J and Shimizu K: "A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner"Biochem Biophys Res Commun. 280. 656-663 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori H, Nomura T, Seno M, Miki Y, Kimura T, Kogami T and Sasaki J: "Expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in rat testis"Acta Histochem Cytochem. 34(1). 25-30 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada T, Nomura T, Miki Y, Kanda S, Sasaski J: "Histochemical and inununohistochemical changes in rat hepatocytes after halothane exposure"J Anesth. 16 (2). 138-144 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kasahara E, Sato EF, Miyoshi M, Konaka R, Hiramoto K, Sasaki J, Tokuda M, Nakano Y and Inoue M: "Role of oxidative stress in germ cell apoptosis induced by di (2-ethylhexyl) phthalate"Biochem J. 365(3). 849-856 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto H, Kawano Y, Nozawa-lnoue K, Aita M, Miki Y, Sasaki J and Maeda T: "The expression of copper, zinc superoxide dismutase (Cu/Zn-SOD) in the rat submandibular gland"Biomed Res. 23(2). 85-90 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura F, Naruishi H, Naruishi K, Yamada T, Sasaki J, Peters C, Uchiyama Y and Murayama Y: "Cathepsin-L, a Key Molecule in the Pathogenesis of Drug-Induced and I-Cell Disease-Mediated Gingival Overgrowth : A Study with Cathepsin-L-Deficient Mice"Am J Pathol. 161 (6). 2047-2052 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wakabayashi T, Kosaka J and Hommura S: "Up regulation of Hrk, a regulator of cell death, in retinal ganglion cells of axotomized rat retina"Neurosc Lett. 318. 77-80 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honda M, Yamada T, Nomura T, Miki Y, Kanda S, Seki A, Sasaki j: "Differential, Histochemical and Immunohistochemical Changes in Rat Hepatocytes after Isoflurane or Sevoflurane Exposure"Acta Med Okayama. 57 (1). 1-12 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hanada H, Katsu K, Kanno T, Sato EF, Kashiwagi A, Sasaki J, Inoue M and Utsumi K: "Cyclosporin A inhibits thyroid hormone-induced shortening of the tadpole tail through membrane permeability transition mechanism"Comp Biochem Physiol. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teruo Yamada et al.: "Histochemical and immunohistochemical changes in rat hepatocytes after halothane exposure"J Anesth. 16. 138-144 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Emiko Kasahara et al.: "Role of oxidative stress in germ cell apoptosis induced by di (2-ethylhexyl) phthalate"Biochem J. 365. 849-856 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hitoshi Yamamoto et al.: "The expression of copper, zinc superoxide dismutase (Cu/Zn-SOD) in the rat submandibular gland"Biomedical Research. 23・2. 85-90 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fusanori Nishimura et al.: "Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth"Am J Pathol. 161・6. 2047-2052 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mayumi Honda et al.: "Differential, histochemical and immunohistochemical changes in rat hepatocytes after isoflurene or sevoflurane exposure"Acta Med Okayama. 57・1. 1-12 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hideki Hanada et al.: "Cyclosporin A inhibits thyroid hormone-induced shortening of the tadpole tail through membrane permeability transition mechanism"Comparative Biochemistry and Physiolgy. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maruyama, K.: "Methylprednisolone accelerates the resolution of glomerulonephritis by sensitizing mesangial cells to apoptosis"Exp.Nephrol.. 9. 317-326 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, S.: "A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner"Biochem.Biophys.Res.Commun.. 280. 656-663 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mori, H.: "Expression of phospholipid hydroperoxide glutathione peroxidase(PHGPx) mRNA in rat testis"Acta Histochem.Cytochem.. 34. 25-30 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada, T.: "Histochemical and immunohistochemical changes in rat hepatocytes after halothane exposure"J.Anesthesia. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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