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Comprehensive elucidation of differentiation and maturation of Sertoli cells and application to reproductive medicine

Research Project

Project/Area Number 17K11204
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionNagoya City University

Principal Investigator

Hayashi Yutaro  名古屋市立大学, 医薬学総合研究院(医学), 教授 (40238134)

Co-Investigator(Kenkyū-buntansha) 安井 孝周  名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153)
水野 健太郎  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70448710)
守時 良演  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (50595395)
西尾 英紀  名古屋市立大学, 医薬学総合研究院(医学), 助教 (10621063)
加藤 大貴  名古屋市立大学, 医薬学総合研究院(医学), 臨床研究医 (00620931)
梅本 幸裕  名古屋市立大学, 医薬学総合研究院(医学), 教授 (80381812)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsセルトリ細胞 / 細胞分化 / インヒビンB / 血液精巣関門 / 医療・福祉 / 発生・分化
Outline of Final Research Achievements

The purpose of the present research is elucidation of molecular biological mechanisms involved in differentiation and maturation of Sertoli cells. We analyzed rat testes histopathologically from immature to pubertal periods. We tried to perform single-cell analyses for the samples derived from primary culture of rat testes, but purification of isolated Sertoli cells remains an issue. We found out the abnormalities of blood-testis barrier and the disorganization of Cldn11 protein that compose tight junction in rat, which received androgen-blockade during fetal period. And, although we also assessed the relationship between serum inhibin B, which reflect the function of Sertoli cells, and testicular tissue in human, we could not recognize significant correlation between them.

Academic Significance and Societal Importance of the Research Achievements

本研究では、思春期以降に形成される血液精巣関門と、その主な構造であるタイトジャンクションの主要な構成タンパク質Cldn11の挙動について一定の成果を得ることができた。すなわち、先天的に精巣が下降しない「停留精巣」の状態では、Cldn11タンパク質の局在・分布に異常が認められ、血液精巣関門がうまく機能しないことを解明した。造精機能障害の主要な原因疾患である停留精巣の組織でこのような変化を捉えられたことから、本研究成果は原因不明であった男性不妊症の病態解明に寄与し、学術的意義あるものと考えられる。こうした知見を治療へ応用できれば不妊に悩むカップルへ福音となるため社会的意義が高い。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (26 results) (of which Int'l Joint Research: 11 results)

  • [Journal Article] Appropriate management of high-flow priapism based on color Doppler ultrasonography findings in pediatric patients: Four case reports and a review of the literature2019

    • Author(s)
      Kato Taiki, Mizuno Kentaro, Nishio Hidenori, Nakane Akihiro, Akita Hidetoshi, Okamura Takehiko, Yasui Takahiro, Hayashi Yutaro
    • Journal Title

      Journal of Pediatric Urology

      Volume: 15 Issue: 2 Pages: 187.e1-187.e6

    • DOI

      10.1016/j.jpurol.2019.01.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dihydrotestosterone induces minor transcriptional alterations in genital skin fibroblasts of children with and without androgen insensitivity2019

    • Author(s)
      Tanase-Nakao Kanako、Mizuno Kentaro、Hayashi Yutaro、Kojima Yoshiyuki、Hara Mariko、Matsumoto Kenji、Matsubara Yoichi、Igarashi Maki、Miyado Mami、Fukami Maki
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 4 Pages: 387-393

    • DOI

      10.1507/endocrj.EJ18-0494

    • NAID

      130007636463

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Testicular teratoma demanded in-depth pathological exploration to rule out malignancy: A pediatric case report2019

    • Author(s)
      Moritoki Yoshinobu, Mizuno Kentaro, Kato Taiki, Hamamoto Shuzo, Hattori Hideo, Ito Yasuhiko, Saitoh Shinji, Yasui Takahiro, Hayashi Yutaro
    • Journal Title

      IJU Case Reports

      Volume: 2 Issue: 3 Pages: 115-115

    • DOI

      10.1002/iju5.12050

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detailed presurgical evaluation of a case of congenital bladder diverticulum2019

    • Author(s)
      Nishio Hidenori、Mizuno Kentaro、Kamisawa Hideyuki、Nakagawa Motoo、Yasui Takahiro、Hayashi Yutaro
    • Journal Title

      Urology Case Reports

      Volume: 27 Pages: 100905-100905

    • DOI

      10.1016/j.eucr.2019.100905

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urothelial carcinoma of the urinary bladder in a 12-year-old girl: A case report with immunohistological analysis and a review of the literature.2018

    • Author(s)
      Kato Taiki, Mizuno Kentaro, Naiki Taku, Nishio Hidenori, Iida Keitaro, Moritoki Yoshinobu, Ando Ryosuke, Okada Atsushi, Yasui Takahiro, Hayashi Yutaro
    • Journal Title

      Urology Case Reports

      Volume: 17 Pages: 29-31

    • DOI

      10.1016/j.eucr.2017.12.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of syringomyelia with lower urinary tract dysfunction in anterior sacral meningocele with a tethered spinal cord: A case report and literature summary.2018

    • Author(s)
      Kato T, Moritoki Y, Mizuno K, Nakagawa M, Goro K, Yasui T.
    • Journal Title

      International Journal of Urology

      Volume: 25 Issue: 5 Pages: 515-516

    • DOI

      10.1111/iju.13534

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Can lichen sclerosus be diagnosed by preputial appearance or symptoms.2018

    • Author(s)
      Kato Taiki, Mizuno Kentaro, Nishio Hidenori, Moritoki Yoshinobu, Nakane Akihiro, Kurokawa Satoshi, Kamisawa Hideyuki, Maruyama Tetsuji, Yasui Takahiro, Hayashi Yutaro
    • Journal Title

      Research and Reports in Urology

      Volume: 10 Pages: 89-94

    • DOI

      10.2147/rru.s173184

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of xenobiotic biomarkers CYP1 family in preputial tissue of patients with hypospadias and phimosis and its association with DNA methylation level of SRD5A2 minimal promoter.2018

    • Author(s)
      Ohsako S, Aiba T, Miyado M, Fukami M, Ogata T, Hayashi Y, Mizuno K and Kojima Y.
    • Journal Title

      Arch Environ Contam Toxicol.

      Volume: 74 Issue: 2 Pages: 240-247

    • DOI

      10.1007/s00244-017-0466-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming patients.2017

    • Author(s)
      Unno Rei, Taguchi Kazumi, Okada Atsushi, Ando Ryosuke, Hamamoto Shuzo, Kubota Yasue, Zuo Li, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
    • Journal Title

      International Journal of Urology

      Volume: 24 Issue: 1 Pages: 75-81

    • DOI

      10.1111/iju.13242

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] New steps of robot-assisted radical prostatectomy using the extraperitoneal approach: a propensity-score matched comparison between extraperitoneal and transperitoneal approach in Japanese patients2017

    • Author(s)
      Kurokawa S, Umemoto Y, Mizuno K, Okada A, Nakane A, Nishio H, Hamamoto S, Ando R, Kawai N, Tozawa K, Hayashi Y, Yasui T
    • Journal Title

      BMC Urology

      Volume: 17 Issue: 1 Pages: 106-114

    • DOI

      10.1186/s12894-017-0298-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of the bone morphogenic protein/SMAD signaling pathway in the etiology of congenital anomalies of the kidney and urinary tract accompanied by cryptorchidism2017

    • Author(s)
      Mizuno Kentaro、Nakane Akihiro、Nishio Hidenori、Moritoki Yoshinobu、Kamisawa Hideyuki、Kurokawa Satoshi、Kato Taiki、Ando Ryosuke、Maruyama Tetsuji、Yasui Takahiro、Hayashi Yutaro
    • Journal Title

      BMC Urology

      Volume: 17 Issue: 1 Pages: 1-6

    • DOI

      10.1186/s12894-017-0300-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 停留精巣の造精障害に対する成育医療:補助生殖医療2019

    • Author(s)
      岩月正一郎、西尾英紀、水野健太郎、梅本幸裕、安井孝周、林祐太郎
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 精巣温度環境における精子幹細胞活性の変動についての培養細胞株研究2019

    • Author(s)
      神沢英幸、水野健太郎、西尾英紀、安井孝周、林祐太郎
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 思春期の停留精巣モデルラットにおける血液精巣関門関連タンパクの発現解析2019

    • Author(s)
      加藤大貴、水野健太郎、西尾英紀、中根明宏、丸山哲史、安井孝周、林祐太郎
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 当科における小児精巣腫瘍10例の臨床的検討2019

    • Author(s)
      西尾英紀、水野健太郎、内木拓、中根明宏、河合憲康、戸澤啓一、安井孝周、林祐太郎
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Lower number of germ cells and serum inhibin-B levels in bilateral cryptorchidism than in unilateral cryptorchidism2019

    • Author(s)
      Kato Taiki, Mizuno Kentaro, Nishio Hidenori, Kamisawa Hideyuki, Kurokawa Satoshi, Nakane Akihiro, Maruyama Tetsuji, Yasui Takahiro, Hayashi Yutaro
    • Organizer
      The Societies for Pediatric Urology 67th Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spermatogonial stem cell activity and indication for surgery of retractile testes2019

    • Author(s)
      Kamisawa Hideyuki, Mizuno Kentaro, Kato Taiki, Nishio Hidenori, Kurokawa Satoshi, Nakane Akihiro, Maruyama Tetsuji, Yasui Takahiro, Hayashi Yutaro
    • Organizer
      The Societies for Pediatric Urology 67th Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 停留精巣における造精機能の回復を目指した基礎的研究~ヒストン修飾による精子幹細胞分化機序の解明~2019

    • Author(s)
      西尾英紀、水野健太郎、丸山哲史、林祐太郎
    • Organizer
      第28回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 思春期停留精巣モデルラットにおける血液精巣関門構成タンパクClaudin11の局在と精細胞の分化との関連2019

    • Author(s)
      加藤大貴、水野健太郎、西尾英紀、安井孝周、林祐太郎
    • Organizer
      第28回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Tips and tricks of the koyanagi procedure for severe proximal hypospadias, how to reduce the complications rate.2018

    • Author(s)
      Hayashi Y, Mizuno K, Nishio H, Kato T
    • Organizer
      29th Congress of the ESPU
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of retained tests in adolescent 46XY patients with complete androgen insensitivity syndrome2018

    • Author(s)
      Moritoki Y, Kato T, Mizuno K, Yasui T, Hayashi Y
    • Organizer
      16th Urological Association of Asia Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Testicular histopathology of male infertility with past history of cryptorchidism2018

    • Author(s)
      Kamisawa H, Kawase K, Nishio H, Iwatsuki S, Umemoto Y, Yasui T, Hayashi Y
    • Organizer
      16th Urological Association of Asia Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The evaluation of contralateral processus vaginalis in laparoscopic surgery for unilateral nonpalpable testis2018

    • Author(s)
      Nishio H, Iwatsuki S, Umemoto Y, Mizuno K, Yasui T, Hayashi Y
    • Organizer
      16th Urological Association of Asia Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Correlation of spermatogonial stem cells with inihibin-B in infant boys with unilateral undescended testes2018

    • Author(s)
      Kato T, Mizuno K, Moritoki Y, Yasui T, Hayashi Y.
    • Organizer
      16th Urological Association of Asia Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinical algorithm for infants with congenital grade 3 hydronephrosis by SFU classification: a retrospective study2018

    • Author(s)
      Nakane A, Moritoki Y, Mizuno K, Yasui T, Hayashi Y
    • Organizer
      16th Urological Association of Asia Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] What is the best exam to detect crossing vessels and ureteral polyps of ureteropelvic junction obstraction? - Comparison between CT and doppler ultrasonography-2018

    • Author(s)
      Kurokawa S, Moritoki Y, Mizuno K, Yasui T, Hayashi Y
    • Organizer
      16th Urological Association of Asia Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 停留精巣の基礎研究~エピジェネティックな精子幹細胞分化障害からみた停留精巣における造精機能障害の解明~2018

    • Author(s)
      西尾英紀、水野健太郎、丸山哲史、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 尿道下裂患者の精巣機能~思春期を迎えた患者の内分泌学的解析から~2018

    • Author(s)
      岩月正一郎、西尾英紀、水野健太郎、梅本幸裕、加藤大貴、安井孝周、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 精原細胞株GC-1を用いた精巣温度環境と精子幹細胞活性の検討2018

    • Author(s)
      神沢英幸、水野健太郎、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 尿道形成に関わる遺伝子群の網羅的発現解析2018

    • Author(s)
      黒川覚史、水野健太郎、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 片側停留精巣患者における不妊症発症に関わる臨床病理的検討~血清InhibinB値と精子幹細胞の関連~2018

    • Author(s)
      加藤大貴、水野健太郎、西尾英紀、安井孝周、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 会陰部異所性精巣の1例~精巣組織と精巣導帯の病理生理学的解析~2018

    • Author(s)
      加藤大貴、水野健太郎、西尾英紀、安井孝周、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 精巣組織からセルトリ細胞を分離・精製する実験手技の確立~停留精巣における造精機能障害の原因究明を目指して~2018

    • Author(s)
      加藤大貴、水野健太郎、西尾英紀、安井孝周、林祐太郎
    • Organizer
      第27回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Gene function analysis of Kdm5a, a histone demethylase, in testicular dysfunction2017

    • Author(s)
      Nishio Hidenori, Mizuno Kentaro, Kato Taiki, Moritoki Yoshinobu, Umemoto Yukihiro, Hayashi Yutaro, Yasui Takahiro
    • Organizer
      第105回日本泌尿器科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 小児泌尿器科学の基礎研究の未来を拓く2017

    • Author(s)
      水野健太郎、西尾英紀、守時良演、加藤大貴、林祐太郎、安井孝周
    • Organizer
      第105回日本泌尿器科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Kdm5a inhibits gonocyte differentiation to spermatogonial stem cells by suppressing Ret gene function via epigenetic regulation2017

    • Author(s)
      Nishio Hidenori, Kato Taiki, Mizuno Kentaro, Moritoki Yoshinobu, Kamisawa Hideyuki, Kurokawa Satoshi, Nakane Akihiro, Maruyama Tetsuji, Hayashi Yutaro, Yasui Takahiro
    • Organizer
      American Urological Association Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Testicular histology in infants with prader-willi syndrome2017

    • Author(s)
      Kato Taiki, Mizuno Kentaro, Nishio Hidenori, Moritoki Yoshinobu, Nakane Akihiro, Kamisawa Hideyuki, Kurokawa Satoshi, Maruyama Tetsuji, Yasui Takahiro, Hayashi Yutaro
    • Organizer
      American Urological Association Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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