• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Androgen-regulated ECM remodeling during sexual differentiation of external genitalia

Research Project

Project/Area Number 18K06837
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionWakayama Medical University

Principal Investigator

Suzuki Kentaro  和歌山県立医科大学, 先端医学研究所, 准教授 (20404345)

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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアンドロゲン / 性差 / 細胞外マトリックス / MMP / 外生殖器 / 細胞外マトリクス / Mmp / sexome / SEXOME / ECM / 器官形成 / 性差形成 / 間葉
Outline of Final Research Achievements

Androgen is a master regulator to induce sexual differences between male and female. This study identified androgen-regulated Mmp (matrix metalloproteinase) is required for establishment of external genital sex differences. This Mmp was expressed dominantly in male genital tubercle (GT), an anlage of external genitalia, and its substrate also showed male-biased expression during sex differentiation of external genitalia. Inhibitory experiment by using tissue organotypic slice culture system showed that this Mmp lead to ECM remodeling in GT mesenchyme and it was required for male-biased mesenchymal cell migration. Furthermore, its expression was regulated in a androgen-AP1 dependent manner.

Academic Significance and Societal Importance of the Research Achievements

アンドロゲンが性差形成に不可欠であることは自明である。しかし、どのような遺伝子を介してどうやって性差を形成しているのか、アンドロゲンによる性差形成機構の解明には至っていない。
これまで報告してきた細胞増殖の性差、細胞骨格の性差、細胞挙動の性差に加え、本研究からECMリモデリングがアンドロゲンによる性差形成に必要な新たなプロセスであることを明らかにした。今回同定したMmpは、外生殖器以外の器官においても発現しており、様々ながんで高発現していることが報告されている。本研究から得られた知見は、外生殖器の性差形成のみならず病態の性差形成機構を理解する上でも有用な知見である。

Report

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

    (20 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Sexual fate of murine external genitalia development: conserved transcriptional competency for male-biased genes in both sexes.2021

    • Author(s)
      Kajioka D, Suzuki K, Matsushita S, Hino S, Sato T, Takada S, Isono K, Takeo T, Kajimoto M, Nakagata N, Nakao M, Suyama M, DeFalco T, Miyagawa S, Yamada G.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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] 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] 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] 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] 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
      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
      2018 Research-status Report
    • Peer Reviewed
  • [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] Single Nucleotide Polymorphisms of HAAO and IRX6 Genes as Risk Factors for Hypospadias.2019

    • Author(s)
      Kojima Y, Koguchi T, Mizuno K, Sato Y, Hoshi S, Hata J, Nishio H, Hashimoto D, Matsushita S, Suzuki K, Miyagawa S, Hui CC, Tanikawa C, Murakami Y, Yamada G, Hayashi Y, Matsuda K.
    • Journal Title

      J Urol.

      Volume: 201(2) Issue: 2 Pages: 386-392

    • DOI

      10.1016/j.juro.2018.07.050

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 微小管の安定化にみられる性差とその意義2021

    • Author(s)
      鈴木 堅太郎、アセベド アルビン、アルカンタラ メリッサ、梶本 みずき、上田 裕子、 梶岡 大暉、山田 源
    • Organizer
      第5回 メカノバイオロジー学会 オンライン開催
    • Related Report
      2020 Annual Research Report
  • [Presentation] 先天異常の発症メカニズムを探る ―生殖器研究からのアプローチ―2020

    • Author(s)
      鈴木堅太郎
    • Organizer
      第60回日本先天異常学会学術集会 オンライン開催
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 外生殖器性差形成過程におけるアンドロゲン標的因子の探索2020

    • Author(s)
      鈴木堅太郎
    • Organizer
      日本アンドロロジー学会第39回学術大会、金沢
    • Related Report
      2020 Annual Research Report
  • [Presentation] アンドロゲンによる細胞骨格制御は、尿道形成に不可欠である2019

    • Author(s)
      鈴木堅太郎
    • Organizer
      日本アンドロロジー学会第38回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス外生殖器組織スライス器官培養系からみえてきたアンドロゲン依存性の器官形成メカニズム2019

    • Author(s)
      鈴木堅太郎
    • Organizer
      第46回日本毒性学会学術年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Mesenchymal-derived actomyosin contractility is required for the tissue fusion during tubular urethral formation in mice2019

    • Author(s)
      Suzuki Kentaro
    • Organizer
      13th World Congress of The International Cleft Lip and Palate Foundation CLEFT2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of sex-biased directional cell migration during organogenesis2019

    • Author(s)
      鈴木堅太郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] アンドロゲン依存性の尿道形成モデル実験システムの構築2018

    • Author(s)
      鈴木堅太郎
    • Organizer
      日本アンドロロジー学会第37回学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] アンドロゲン依存性のマウス胎仔外生殖器組織培養実験システムの構築2018

    • Author(s)
      鈴木堅太郎
    • Organizer
      日本毒性学会2018年度学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Establishment of the Embryonic External Genitalia Slice Culture System: Analysis of mechanism of androgen-induced urethral masculinization.2018

    • Author(s)
      Kentaro Suzuki
    • Organizer
      8th International Symposium on Vertebrate Sex Determination
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi