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Establishment of the differentiation method to spermatogenesis by the xenogeneic transplantation of spermatogonia stem cells and the in vitro culture

Research Project

Project/Area Number 24590243
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionTokyo Medical University

Principal Investigator

Qu Ning  東京医科大学, 医学部, 講師 (70527952)

Co-Investigator(Kenkyū-buntansha) ITOH Masahiro  東京医科大学, 医学部, 教授 (00232471)
YOSHIMOTO Takayuki  東京医科大学, 医学部, 教授 (80202406)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords精子形成 / 精子幹細胞 / 異種移植 / 免疫寛容 / マウス / 精巣 / マクロファージ / サイトカイン / 抗がん剤 / 移植 / 免疫抑制
Outline of Final Research Achievements

There have been increasing reports on xenogeneic transplantation of mammalian male spermatogonial stem cells (SSCs). However, in most previous studies on xenogeneic SSCs transplantation, to avoid immunologic rejection, immunodeficient or immunosuppressed mice were used as the recipients, which were pre-treated with busulfan (Myleran, 1,4-butanediol methanesulfonate) for depletion of endogenous germ cells before the SSCs transplantation. This study demonstrated that in the testes of busulfan-treated immune-competent mice, the increase of TNF-a in the seminiferous tubule and the infiltration of the macrophage were seen in the interstitium, and the increase of apoptotic cytokine such as Fas,FasL,caspase8 and the decrease of caspase9 were detected. Furthermore, it was revealed that immune-suppressive cytokines and M2 macrophage in the testis are related with testicular immune privileged circumstances.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (28 results)

All 2016 2015 2014 2013 2012

All Journal Article (15 results) (of which Peer Reviewed: 14 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (13 results) (of which Invited: 2 results)

  • [Journal Article] Low-dose exposure to di-(2-ethylhexyl) phthalate (DEHP) increases susceptibility to testicular autoimmunity in mice.2015

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

      Reproductive Biology

      Volume: 15(3) Issue: 3 Pages: 163-171

    • DOI

      10.1016/j.repbio.2015.06.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scimitar vein descending from the right inferior lobe to the inferior vena cava beneath the diaphragm: a rare case.2015

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

      Anatomical Science International

      Volume: 90(2) Issue: 2 Pages: 123-125

    • DOI

      10.1007/s12565-014-0230-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 炎症疾患におけるTh17関連サイトカインIL-17,IL-22,IL-23の役割2015

    • Author(s)
      徐明利、曲 寧、溝口出、古澤純一、千葉祐規乃、伊藤正裕、善本隆之
    • Journal Title

      炎症と免疫

      Volume: 23(2) Pages: 66-72

    • Related Report
      2015 Annual Research Report
  • [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: 90 Issue: 4 Pages: 264-274

    • DOI

      10.1007/s12565-014-0261-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / 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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access / 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 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases.2013

    • Author(s)
      Qu N, Xu M, Mizoguchi I, Furusawa J, Kaneko K, Watanabe K, Mizuguchi J, Itoh M,Kawakami Y, Yoshimoto T.
    • Journal Title

      Clin Dev Immunol.

      Volume: 2013:968549 Pages: 1-13

    • DOI

      10.1155/2013/968549

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lymphangiogenesis in chronic inflammation in the testis2013

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

      Andrology

      Volume: 1(1) Pages: 147-154

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cadmium exposure increases susceptibility to testicular autoimmunity in mice2013

    • 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

      J Appl Toxicol

      Volume: 33(7) Pages: 652-660

    • 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 mice.2013

    • 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

      J Reprod Dev

      Volume: 59(5) Pages: 485-490

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The effects of adjuvants on autoimmune responses against testicular antigens in mice.2013

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

      J Reprod Dev

      Volume: 59(2) Pages: 139-144

    • 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

      Reprod Fert Develop

      Volume: 24 Pages: 337-343

    • 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: 824-31

    • 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

      Med Mol Morphol

      Volume: 45(1) Pages: 35-44

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 精巣におけるマクロファージの免疫寛容機構2016

    • Author(s)
      曲   寧,寺山 隼人, 平井 宗一, 林 省吾、畑山 直之,倉升 三幸, 小川 夕輝, 坂部 貢, 伊藤 正裕
    • Organizer
      第121回日本解剖学会・全国学術集会
    • Place of Presentation
      福島
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ラットにおける異所性精巣移植の試み2016

    • Author(s)
      畑山 直之,曲   寧,林 省吾,平井 宗一,、倉升 三幸, 永堀 健太,小川 夕輝, 伊藤 正裕
    • Organizer
      第121回日本解剖学会・全国学術集会
    • Place of Presentation
      福島
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Goshajinkigan completely recover the severe aspermatogenesis after busulfan treatment in mice2015

    • Author(s)
      Qu N, Hirayanagi Y, Hayashi S, Hirai S, Hatayama N, Kuramasu M, Ogawa Y, Naito M, Itoh M
    • Organizer
      第120回日本解剖学会・全国学術集会  第92回 日本生理学会大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status 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 Research-status Report
  • [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
      2014-12-12 – 2014-12-13
    • Related Report
      2014 Research-status Report
  • [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 Research-status Report
  • [Presentation] Traditional oriental Chinese medicine protects against busulfan-induce male infertility in mice2014

    • Author(s)
      Qu N, Hirayanagi Y, Kuramasu M, Hayashi S, Hirai S, Hatayama N, Ogawa Y, Naito M, Itoh M
    • Organizer
      第119回日本解剖学会・全国学術集会
    • Place of Presentation
      栃木
    • Related Report
      2013 Research-status Report
  • [Presentation] Mono-(2-ethylhexyl) phthalate on drug transporter, P-glycoprotein (MDR1), in the testis of prepubertal rats2014

    • Author(s)
      内藤 宗和, 平井 宗一, 曲   寧, 林  省吾, 畑山 直之, 小川 夕輝, 倉升 三幸, 河田 晋一, 伊藤 正裕
    • Organizer
      第119回日本解剖学会・全国学術集会
    • Place of Presentation
      栃木
    • 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器系への影響2014

    • Author(s)
      平栁 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119回日本解剖学会・全国学術集会
    • Place of Presentation
      栃木
    • 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] Autoimmune responses induced by immunization with xenogenic testicular germ cells alone2012

    • Author(s)
      Qu N,Terayama H, Hirai S, Hirayanagi Y, Naito M, Itoh M
    • 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] EBI3(Epstein-Barr virus-induced gene-3) ノックアウトマウスにおける精巣免疫微小環境について2012

    • Author(s)
      寺山 隼人, 平井 宗一, 曲   寧, 畑山 直之, 平柳 淑恵, 内藤 宗和, 善本 隆之, 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

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Published: 2013-05-31   Modified: 2019-07-29  

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