Analyses for vascular formation during androgen dependent sexual development

• Project/Area Number: 17K08495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Iwate Medical University
• Principal Investigator: Murashima Aki 岩手医科大学, 医学部, 助教 (50637105)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 性分化 / 血管形成 / アンドロゲン / 中腎 / マウス / 発生学 / 血管

Outline of Final Research Achievements

This study tried to clarify the anatomical basis of vascular development during hormone-dependent sexual differentiation. Spatio-temporal analysis of vascular development demonstrated sexual dimorphic patters of venous return during early sexual differentiation of the mesonephros. Cell lineage analyses further suggested vascular endothelial cells showing dimorphic pattern possess site-specific origin and different androgen responsiveness. These results are revealing novel insights into the early sexual dimorphism in vascular development and signal pathway of androgen required for the secondary masculinization of the reproductive organs.

Academic Significance and Societal Importance of the Research Achievements

血管形成は胚発生において基盤を担うと考えられ、Sry遺伝子依存的に性的二型を示すマウス生殖腺においては、雄特有、あるいは雌特有の血管構造が構築されることがその形態形成に必要不可欠である。一方で生殖腺に隣接し、アンドロゲン依存的雄性化を示す中腎領域における血管構造の性差の有無、そしてその機能については、ほとんど報告されていなかった。本研究によって、中腎領域における初期の性的二型とその起源が明らかになるとともに、二次的な雄化に必要なアンドロゲンの伝達（循環）経路の血管形成における特性に関しても明らかとなりつつあり、解剖学、発生学分野に貢献するものであると考える。

Research Products

• [Int'l Joint Research] Chinese Academy of Sciences/NIBS(China)
• [Journal Article] New Insights into Development of Female Reproductive Tract-Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development (2021)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Radiation inducible MafB gene is required for thymic regeneration (2021)
  • 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 Yamada1
  • Journal Title: Scientific Reports Volume: - Issue: 1 Pages: 10439-10439
  • DOI: 10.1038/s41598-021-89836-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of masculinization: androgen signalling for external genitalia development (2018)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] マウス初期胚の眼球形成領域の血管形成 (2017)
  • Author(s): 清野太郎，木村英二，村嶋亜紀，黒坂大次郎
  • Journal Title: 岩手医学雑誌 Volume: 69(5) Pages: 243-253
  • NAID: 40021420246
• [Journal Article] Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis (2017)
  • Author(s): Liu Liqing、Suzuki Kentaro、Chun Eunice、Murashima Aki、Sato Yuki、Nakagata Naomi、Fujimori Toshihiko、Yonemura Shigenobu、He Wanzhong、Yamada Gen
  • Journal Title: Sexual Development Volume: 11 Issue: 4 Pages: 190-202
  • DOI: 10.1159/000477452
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Developmental Contribution of Wnt-signal-responsive Cells to Mouse Reproductive Tract Formation (2017)
  • Author(s): Haraguchi Ryuma, Kitazawa Riko, Murashima Aki, Yamada Gen, Kitazawa Sohei
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 50 Issue: 4 Pages: 127-133
  • DOI: 10.1267/ahc.17017
  • NAID: 130006003857
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 薬剤誘導型遺伝子改変マウスを用いた頭部血管発生機構の解析 (2019)
  • Author(s): 村嶋亜紀、及川里百合、木村英二、人見次郎
  • Organizer: 第124回 日本解剖学会総会・全国学術集会
• [Book] 小児泌尿器科学 (2021)
  • Author(s): 日本小児泌尿器科学会
  • Total Pages: 368
  • Publisher: 診断と治療社
  • ISBN: 4787824228
• [Book] 生殖生理 第7章 性分化 (2019)
  • Author(s): 大須賀 穣、藤井知行
  • Total Pages: 330
  • Publisher: 中山書店
  • ISBN: 9784521747613
• [Book] 生殖生理（分担執筆） (2019)
  • Author(s): 大須賀 穣、藤井知行 （編集）
  • Total Pages: 330
  • Publisher: 中山書店
  • ISBN: 9784521747613