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Molecular developmental analysis on erectile tissue formation

Research Project

Project/Area Number 18K06938
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionWakayama Medical University

Principal Investigator

Gen Yamada  和歌山県立医科大学, 先端医学研究所, 教授 (80174712)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords海綿体 / 男性ホルモン / シヌソイド / 勃起 / 平滑筋 / 二光子顕微鏡 / 培養系 / ストレス応答 / 血管形成 / 生殖器 / 間葉細胞 / 雄性化 / 男性ホルモンレセプター(AR) / VEGF / 男性ホルモンレセプター(AR) / ED
Outline of Final Research Achievements

In the upper (dorsal) part of penis, corpus cavernosum (CC) plays fundamental roles for erection. The basis of ED by penile abnormality is poorly understood. To analyze the 3D structure of murine CC sinusoid, 3D reconstruction was performed. Sinusoids prominently developed adjacent to tunica albuginea. As for pathogenic signaling, aged samples contained ectopic chondrocytes and the expression of SOX9, chondrogenic regulator, was upregulated and the expression of RBPJ, the Notch signal regulator, was downregulated. Furthermore, a novel in vitro explant system to analyze the dynamic erectile contraction/relaxation was established. The data show regulatory contraction/relaxation processes by phenylephrine (PE) and nitric oxide (NO) donor. Two photon excitation microscopy (TPEM) observation shows the synchronous movement of sinusoidal space and the CC. The model enables to directly analyze various stressed conditions.

Academic Significance and Societal Importance of the Research Achievements

勃起不全(ED)は、高齢化から増加している。海綿体の研究は、生理学的実験等が主体であり、その構造と動態に関する研究は希少であった。本研究ではマウスexplant(組織片)による新規な培養を行い、海綿体発生や機能に関する制御因子群の解明、男性ホルモン系との関連を解明した。その結果PEやSNPによる収縮/弛緩反応の誘導が可能となり、バイアグラなどの薬剤添加により弛緩機能の変化を直接評価することができた。これらはシヌソイドを含む、微細で高度な血管系を基盤とする疾患の理解に有用と考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (13 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 9 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Remarks (2 results)

  • [Int'l Joint Research] University of Toronto(カナダ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Baskin Lab, UCSF/Baylor College of Medicine/NIH(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] UP, Diliman(フィリピン)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] The University of Bonn(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] 3D reconstruction and histopathological analyses on murine corporal body.2021

    • Author(s)
      Hashimoto D, Kajimoto M, Ueda Y, Hyuga T, Fujimoto K, Inoue S, Suzuki K, Kataoka T, Kimura K, Yamada G.
    • Journal Title

      Reprod Med Biol.

      Volume: 20(2) Issue: 2 Pages: 199-207

    • DOI

      10.1002/rmb2.12369

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] New Insights into Development of Female Reproductive Tract-Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development2021

    • Author(s)
      Haraguchi Ryuma、Yamada Gen、Murashima Aki、Matsumaru Daisuke、Kitazawa Riko、Kitazawa Sohei
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1211-1211

    • DOI

      10.3390/ijms22031211

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic erectile responses of a novel penile organ model utilizing TPEM.2021

    • Author(s)
      Hashimoto D, Hirashima T, Yamamura H, Kataoka T, Fujimoto K, Hyuga T, Yoshiki A, Kimura K, Kuroki S, Tachibana M, Suzuki K, Yamamoto N, Morioka S, Sasaki T, Yamada G.
    • Journal Title

      Biol Reprod.

      Volume: in press Issue: 4 Pages: 875-886

    • DOI

      10.1093/biolre/ioab011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation inducible MafB gene is required for thymic regeneration2021

    • Author(s)
      Daiki Hashimoto, Jose Gabriel R. Colet, Aki Murashima, Kota Fujimoto, Yuko Ueda, Kentaro Suzuki, Taiju Hyuga, Hiroaki Hemmi, Tsuneyasu Kaisho, Satoru Takahashi, Yousuke Takahama and Gen Yamada
    • Journal Title

      Scientific Report

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sexual fate of murine external genitalia development: conserved transcriptional competency for male-biased genes in both sexes.2021

    • Author(s)
      Daiki Kajioka ,Kentaro Suzuki,Shoko Matsushita,Shinjiro Hino,Tetsuya Sato ,Shuji Takada,Kyoichi Isono,Toru Takeo,Mizuki Kajimoto,Naomi Nakagata ,Mitsuyoshi Nakao,Mikita Suyama,Tony DeFalco,Shinichi Miyagawa ,Gen Yamada.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of surgical procedures of mouse urethra by visualization and the formation of fistula2020

    • Author(s)
      Hyuga Taiju、Hashimoto Daiki、Matsumaru Daisuke、Kumegawa Shinji、Asamura Shinichi、Suzuki Kentaro、Katayama Kei-ichi、Nakamura Shigeru、Nakai Hideo、Yamada Gen
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 18251-18251

    • DOI

      10.1038/s41598-020-75184-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.2019

    • Author(s)
      Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G.
    • Journal Title

      Commun. Biol.

      Volume: eCollection Issue: 1 Pages: 95-95

    • DOI

      10.1038/s42003-019-0336-3

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth.2019

    • Author(s)
      Kajioka D, Suzuki K, Nakada S, Matsushita S, Miyagawa S, Takeo T, Nakagata N, Yamada G.
    • Journal Title

      Congenit. Anom. (Kyoto)

      Volume: in press Issue: 1 Pages: 0-0

    • DOI

      10.1111/cga.12326

    • NAID

      210000012752

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulatory roles of epithelial-mesenchymal interaction (EMI) during early and androgen dependent external genitalia development2019

    • Author(s)
      Hyuga T, Suzuki K, Acebedo AR, Hashimoto D, Kajimoto M, Miyagawa S, Enmi JI, Yoshioka Y, Yamada G.
    • Journal Title

      Differentiation

      Volume: 110 Pages: 29-35

    • DOI

      10.1016/j.diff.2019.08.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hedgehog Signaling for Urogenital Organogenesis and Prostate Cancer: An Implication for the Epithelial?Mesenchyme Interaction (EMI)2019

    • Author(s)
      Hyuga Taiju、Alcantara Mellissa、Kajioka Daiki、Haraguchi Ryuma、Suzuki Kentaro、Miyagawa Shinichi、Kojima Yoshiyuki、Hayashi Yutaro、Yamada Gen
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 1 Pages: 58-58

    • DOI

      10.3390/ijms21010058

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Developmental mutant mouse models for external genitalia formation.2019

    • Author(s)
      Hashimoto D, Hyuga T, Acebedo AR, Alcantara MC, Suzuki K, Yamada G.
    • Journal Title

      Congenit. Anom. (Kyoto)

      Volume: 59(3) Issue: 3 Pages: 74-80

    • DOI

      10.1111/cga.12319

    • NAID

      210000012745

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional distinctions associated with the diversity of sex steroid hormone receptors ESR and AR.2018

    • Author(s)
      Ogino Y, Tohyama S, Kohno S, Toyota K, Yamada G, Yatsu R, Kobayashi T, Tatarazako N, Sato T, Matsubara H, Lange A, Tyler CR, Katsu Y, Iguchi T, Miyagawa S.
    • Journal Title

      J Steroid Biochem Mol Biol.

      Volume: 184 Pages: 38-46

    • DOI

      10.1016/j.jsbmb.2018.06.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulation of masculinization: androgen signalling for external genitalia development2018

    • Author(s)
      Matsushita Shoko、Suzuki Kentaro、Murashima Aki、Kajioka Daiki、Acebedo Alvin Resultay、Miyagawa Shinichi、Haraguchi Ryuma、Ogino Yukiko、Yamada Gen
    • Journal Title

      Nature Reviews Urology

      Volume: 印刷中 Issue: 6 Pages: 358-368

    • DOI

      10.1038/s41585-018-0008-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 外生殖器の分子発生メカニズムの解明2019

    • Author(s)
      山田 源
    • Organizer
      日本アンドロロジー学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Molecular mechanisms of external genitalia formation2019

    • Author(s)
      山田 源
    • Organizer
      米ハーバード大 Prof Sean lee Lab
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子改変動物を用いた外生殖器の分子発生メカニズムの解明2019

    • Author(s)
      山田 源
    • Organizer
      第107回 日本泌尿器科学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] “Molicura mechanism of reproductive oregano formation2019

    • Author(s)
      山田 源
    • Organizer
      中国 Shang dong- Wakayama Medical Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 「マウスモデルを用いた生殖器の発生メカニズムの解析;男性ホルモン依存性の発生制御機構」2018

    • Author(s)
      山田 源
    • Organizer
      第2回細胞内シグナル応答研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 「マウス外部生殖器のアンドロゲンによる発生制御機構;新しい器官培養系によるアッセイ系について」2018

    • Author(s)
      山田 源
    • Organizer
      第42回関西生殖発生毒性フォーラム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] "Molecular mechanisms of ext. genitalia formation; An attractive model for Epi-mesenchymal interaction and androgen-driven organogenesis"2018

    • Author(s)
      山田 源
    • Organizer
      Biocenter Oulu, Laboratory of Developmental Biology, Oulu University
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] "The molecular mechanisms of genital development; Candidate signal to cytoskeletal components in male-type organogenesis"2018

    • Author(s)
      山田 源
    • Organizer
      Institute of Biotechnology, University of Helsinki
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] Department of Developmental Genetics, WMU

    • URL

      http://www.wakayama-med.ac.jp/english/undergraduate/medicine/160904/index.html

    • Related Report
      2018 Research-status Report
  • [Remarks] Gen Yamada, Research Gate

    • URL

      https://www.researchgate.net/profile/Gen_Yamada

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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