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Establishment of a highly reproducible model of immunological male infertility with analyses of related testicular autoantigens

Research Project

Project/Area Number 23500504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionTokyo Medical University

Principal Investigator

ITOH Masahiro  東京医科大学, 医学部, 教授 (00232471)

Co-Investigator(Kenkyū-buntansha) KAWAMOTO Eiichi  東京医科大学, 医学部, 准教授 (20074718)
SASAKI Hiraku  順天堂大学, スポーツ健康科学部, 助教 (20384969)
NAITO Munekazu  愛知医科大学, 医学部, 准教授 (10384984)
QU Ning  東京医科大学, 医学部, 講師 (70527952)
HIRAI Shuichi  東京医科大学, 医学部, 講師 (70516054)
TERAYAMA Hayato  東海大学, 医学部, 講師 (00384983)
HAYASHI Shogo  東京医科大学, 医学部, 准教授 (60349496)
IKEDA Ayumi  東京医科大学, 医学部, 助教 (90617515)
HATAYAMA Naoyuki  東京医科大学, 医学部, 助教 (80534792)
Research Collaborator OGAWA Yuki  
KURAMASU Miyuki  
HIRAYANAGI Yoshie  
KUERBAN Maimaiti  
MUSHA Muhetaerjiang  
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords精子形成 / 自己免疫性精巣炎 / 自己抗原 / タンパク質同定 / マウス / 精子抗原 / 精巣 / 自己免疫疾患 / 抗原解析 / 精巣上体
Outline of Final Research Achievements

Experimental autoimmune orchitis (EAO) is one of the models of immunological male infertility. To establish a highly reproducible model of EAO, in 2011, we found that only one placement of a syngeneic donor’s testes, epididymides and vasa deferentia into the abdominal cavity was sufficient to induce EAO on the recipient’s testes in mice. It was also noted that the placement of testes, epididymides and vasa deferentia induced only orchitis without epididymo-vasitis. At the next three years, the testicular autoantigens were identified using sera obtained from EAO-affected mice. The testicular proteins were separated using two-dimensional gel electrophoresis, and the autoantigens proteins were identified by Western blotting and Mass spectrometry. Some identified testicular specific autoantigens have not been reported previously, and the clarification of these proteins will facilitate new approaches for understanding EAO.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (29 results)

All 2015 2014 2013 2012 2011

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 1 results,  Acknowledgement Compliant: 4 results) Presentation (15 results) (of which Invited: 2 results)

  • [Journal Article] Busulfan pretreatment for transplantation of rat spermatogonia differentially affects immune and reproductive systems in male recipient mice.2015

    • Author(s)
      Hirayanagi Y, Qu N, Hirai S, Naito M, Terayama H, Hayashi S, Hatayama N, Kuramasu M, Ogawa Y, Itoh M.
    • Journal Title

      Anat Sci Int.

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Contribution of IL-12/IL-35 common subunit p35 to maintaining the testicular immune privilege2014

    • Author(s)
      Terayama H, Yoshimoto T, Hirai S, Naito M, Qu N, Hatayama N, Hayashi S, Mitobe K, Furusawa J, Mizoguchi I, Kezuka T, Goto H, Suyama K, Moriyama H, Sakabe K, Itoh M.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 4 Pages: e96120-e96120

    • DOI

      10.1371/journal.pone.0096120

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chronological changes of delayed-type hypersensitivity in mice immunised with testicular germ cells alone.2014

    • Author(s)
      Qu N, Naito M, Terayama H, Hirai S, Musha M, Itoh M.
    • Journal Title

      Andrologia

      Volume: 46 Issue: 5 Pages: 556-563

    • DOI

      10.1111/and.12116

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Neonatal estrogen treatment with β-estradiol 17-cypionate induces in post-pubertal mice inflammation in the ductuli efferentes, epididymis, and vas deferens, but not in the testis, provoking obstructive azoospermia.2014

    • Author(s)
      Naito M, Hirai S, Terayama H, Qu N, Hayashi S, Hatayama N, Kawamura H, Nakano T, Itoh M.
    • Journal Title

      Med Mol Morphol.

      Volume: 47 Issue: 1 Pages: 21-30

    • DOI

      10.1007/s00795-013-0034-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cadmium exposure increases susceptibility to testicular autoimmunity in mice.2014

    • Author(s)
      Ogawa Y, Itoh M, Hirai S, Suna S, Naito M, Qu N, Terayama H, Ikeda A, Miyaso H, Matsuno Y, Komiyama M, Mori C.
    • Journal Title

      Journal of Applied Toxicology

      Volume: 33(7) Issue: 7 Pages: 652-660

    • DOI

      10.1002/jat.2713

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lymphangiogenesis in chronic inflammation in the testis.2013

    • Author(s)
      Hirai S, Naito M, Terayama H, Qu N, Kuerban M, Musha M, Itoh M.
    • Journal Title

      Andrology

      Volume: 1(1) Issue: 1 Pages: 147-154

    • DOI

      10.1111/j.2047-2927.2012.00015.x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects on the Local Immunity in the Testis by Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) in Mice2013

    • Author(s)
      Kitaoka M, Hirai S, Terayama H, Naito M, Qu N, Hatayama N, Miyaso H, Matsuno Y, Komiyama M, Itoh M, Mori C.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 59 Issue: 5 Pages: 485-490

    • DOI

      10.1262/jrd.2012-180

    • NAID

      130003361051

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Effects of Adjuvants on Autoimmune Responses Against Testicular Antigens in Mice2013

    • Author(s)
      Musha M, Hirai S, Naito M, Terayama H, Qu N, Hatayama N, Itoh M.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 59 Issue: 2 Pages: 139-144

    • DOI

      10.1262/jrd.2012-121

    • NAID

      10031170771

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Xenogeneic and endogenous spermatogenesis following transplantation of rat germ cells into testes of immunocompetent mice.2012

    • Author(s)
      Qu N, Naito M, Li J, Terayama H, Hirai S, Itoh M
    • Journal Title

      Reproduction, Fertility, and Development

      Volume: 24 Issue: 2 Pages: 337-343

    • DOI

      10.1071/rd10349

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of Fas/Fas-L and Bax/Bcl-2 systems in germ cell death following immunization with syngeneic testicular germ cells in mice.2012

    • Author(s)
      Kuerban M, Naito M, Hirai S, Terayama H, Qu N, Ikeda A, Musha M, Koji T, Itoh M
    • Journal Title

      Journal of Andrology

      Volume: 33(5) Pages: 824-831

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Postinflammation stage of autoimmune orchitis induced by immunization with syngeneic testicular germ cells alone in mice.2012

    • Author(s)
      Naito M, Hirai S, Terayama H, Qu N, Kuerban M, Musha M, Kitaoka M, Ogawa Y, Itoh M
    • Journal Title

      Medical Molecular Morphology

      Volume: 45(1) Issue: 1 Pages: 35-44

    • DOI

      10.1007/s00795-011-0539-2

    • NAID

      10030573640

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The effects of adjuvants on autoimmune responses against testicular antigens in mice2012

    • Author(s)
      Musha M, Hirai S, Naito M, Terayama H, Qu N, Hatayama N, Itoh M
    • Journal Title

      Journal of Reproduction and Development

      Volume: 59(2) Pages: 139-144

    • NAID

      10031170771

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Experimental model of autoimmune orchitis with abdominal placement of donor's testes, epididymes and vasa deferentia in recipient mice2011

    • Author(s)
      Hayato Terayama, Masahiro Itoh, Munekazu Naito, Shuichi Hirai, Ning Qu, Maimaiti Kuerban, Muhetaerjiang Musha
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 90(2) Issue: 2 Pages: 195-201

    • DOI

      10.1016/j.jri.2011.03.008

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intratesticular Expression of mRNAs of Both Interferon γ and Tumor Necrosis Factor α is Significantly Increased in Experimental Autoimmune Orchitis in Mice2011

    • Author(s)
      Hayato Terayama, Munekazu Naito, Ning Qu, Shuichi Hirai, Miyuki Kitaoka, Yuki Ogawa, Masahiro Itoh
    • Journal Title

      Journal of Reproduction and Development

      Volume: 57 Issue: 2 Pages: 296-302

    • DOI

      10.1262/jrd.10-121N

    • NAID

      10028275659

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 微量カドミウム曝露は自己免疫障害を増悪させる2014

    • Author(s)
      小川夕輝, 倉升三幸, 曲  寧, 平井宗一, 林 省吾, 畑山直之, 伊藤正裕
    • Organizer
      第29回日本生殖免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] ブスルファン処置マウスの精子形成障害における牛車腎気丸の治療効果2014

    • Author(s)
      曲  寧, 平栁淑恵, 林 省吾, 平井宗一, 畑山直之, 倉升三幸, 小川夕輝, 伊藤正裕
    • Organizer
      第29回日本生殖免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-12 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 進化と発生からみた「ヒト精子の生きにくさ」2014

    • Author(s)
      伊藤 正裕
    • Organizer
      第32回日本受精着床学会総会・学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-31 – 2014-08-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Contribution of IL-35 to maintaining the testicular immune privilege2014

    • Author(s)
      寺山隼人, 内藤宗和, 善本隆之, 平井宗一, 曲 寧, 倉升三幸, 金沢輝久, 隅山香織, 坂部 貢, 伊藤正裕
    • Organizer
      アンドロロジー学会第33回学術大会および第20回精子形成・精巣毒性研究会
    • Place of Presentation
      長野
    • Year and Date
      2014-06-12 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of macrophages in newly formed lymphatic vessels in the testis.2013

    • Author(s)
      Hirai S, Naito M, Terayama H, Qu N, Hatayama N, Musha M, Itoh M.
    • Organizer
      12th International Congress of Reproductive Immunology
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Testicular immune-microenvironment in the Epstein-Barr virus-induced gene-3 (EBI3) knock out mice.2013

    • Author(s)
      Terayama H, Hirai S, Yoshimoto T, Naito M, Qu N, Hatayama N, Sakabe K*, Itoh M.
    • Organizer
      12th International Congress of Reproductive Immunology
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 免疫正常マウスにおけるブスルファンの免疫系と生殖系への影響2013

    • Author(s)
      平柳淑恵, 曲 寧, 平井宗一, 内藤宗和, 倉升三幸, 林 省吾, 畑山直之, 伊藤正裕
    • Organizer
      第20回日本免疫毒性学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 微量カドミウム曝露は自己免疫性精子形成障害を増悪させる2013

    • Author(s)
      小川夕輝, 倉升三幸, 曲 寧, 平井宗一, 林 省吾, 畑山直之, 内藤宗和, 伊藤正裕
    • Organizer
      第20回日本免疫毒性学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 低用量フタル酸曝露による自己免疫性精巣炎誘導への影響2013

    • Author(s)
      内藤宗和, 平井宗一, 曲 寧, 倉升三幸, 小川夕輝, 畑山直之, 林 省吾, 伊藤正裕
    • Organizer
      第28回日本生殖免疫学会総会・学術集会
    • Place of Presentation
      兵庫
    • Related Report
      2013 Research-status Report
  • [Presentation] 精巣とサイトカイン2013

    • Author(s)
      寺山 隼人, 内藤 宗和, 曲 寧, 平井 宗一, 畑山 直之, 伊藤 正裕
    • Organizer
      第118回日本解剖学会総会・学術集会
    • Place of Presentation
      香川
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Autoimmune responses induced by immunization with xenogenic testicular germ cells alone2013

    • Author(s)
      曲 寧, 寺山 隼人, 平井 宗一, 平栁 淑恵. 内藤 宗和, 伊藤 正裕
    • Organizer
      第118回日本解剖学会総会・学術集会
    • Place of Presentation
      香川
    • Related Report
      2012 Research-status Report
  • [Presentation] 後天性精子障害の病態解析 異種生殖細胞に対する免疫正常マウスの精巣組織反応2012

    • Author(s)
      曲 寧, 寺山 隼人, 平井 宗一, 内藤 宗和, 伊藤 正裕
    • Organizer
      第27回日本生殖免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] Autoimmune responses induced by immunization with xenogenic testicular germ cells alone2012

    • Author(s)
      Ning Qu, Hayato Terayama, Shuichi Hirai, Yoshie Hirayanag, Munekazu Naito, Masahiro Itoh
    • Organizer
      日本アンドロロジー学会第31回学術大会ならびに総会および第18回精子形成・精巣毒性研究会 共同開催学会
    • Place of Presentation
      兵庫
    • Related Report
      2012 Research-status Report
  • [Presentation] 異種生殖細胞に対する免疫正常マウスの精巣組織反応2011

    • Author(s)
      曲 寧、内藤宗和、寺山隼人、平井宗一、伊藤正裕
    • Organizer
      第67回日本顕微鏡学会学術講演会(招待講演)
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] 自己免疫性精巣炎における細胞死2011

    • Author(s)
      平井宗一、内藤宗和、寺山隼人、曲 寧、池田あゆみ、伊藤正裕
    • Organizer
      第43回日本臨床分子形態学会総会・学術集会(招待講演)
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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