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Exploring factors that drive sexual differentiation of external genitalia

Research Project

Project/Area Number 18H02474
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionTokyo University of Science

Principal Investigator

MIYAGAWA SHINICHI  東京理科大学, 基礎工学部生物工学科, 准教授 (30404354)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords外生殖器 / アンドロゲン / 性分化 / マウス / 生殖器 / 発生 / ホルモン / 遺伝子発現
Outline of Final Research Achievements

The mechanism of sexual differentiation of the external genitalia, which is regulated by the hormonal environment, remains unclear. In this study, we identified that several parameters that prescribe hormone-dependent development and morphology of external genitalia by computed tomography (CT) scan analysis, and were able to quantitatively evaluate the phenotype of the mouse external genitalia. In addition, gene expression in the fetal external genitalia was analyzed by RNA sequencing, and identified several differential expression genes (DEGs) which gene expression depends on hormonal environment during embryonic development. The results provide a basis for accurate evaluation of the degree of sexual differentiation between males and females at the genetic level.

Academic Significance and Societal Importance of the Research Achievements

尿道下裂の発症頻度は1/200-1/300とされ、非常に頻度の高い先天性疾患である。新生児期の外性器異常は、社会的な性の決定に関わる大きな問題であることから、正確な医学的評価と根拠を要する。本研究によって得られる知見は、生殖器系に係わる診断技術や治療などの医療行為を実践するための基本的知識を提供すると共に、これら先天性疾患の原因解明の基礎となることが期待される。本研究によって推進される性分化や疾患に対する理解は、性の多様性の理解にもつながる。

Report

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

    (24 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 15 results,  Open Access: 7 results) Presentation (6 results) (of which Invited: 3 results)

  • [Int'l Joint Research] Exeter University(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] エクセター大学(英国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] New frontiers of developmental endocrinology opened by researchers connecting irreversible effects of sex hormones on developing organs2021

    • Author(s)
      Iguchi Taisen、Sato Tomomi、Nakajima Tadaaki、Miyagawa Shinichi、Takasugi Noboru
    • Journal Title

      Differentiation

      Volume: 118 Pages: 4-23

    • DOI

      10.1016/j.diff.2020.10.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of G protein‐coupled estrogen receptors in Japanese medaka, Oryzias latipes2020

    • Author(s)
      Miyaoku Kaori、Ogino Yukiko、Lange Anke、Ono Ayaka、Kobayashi Tohru、Ihara Masaru、Tanaka Hiroaki、Toyota Kenji、Akashi Hiroshi、Yamagishi Genki、Sato Tomomi、Tyler Charles R.、Iguchi Taisen、Miyagawa Shinichi
    • Journal Title

      Journal of Applied Toxicology

      Volume: - Issue: 9 Pages: 1390-1399

    • DOI

      10.1002/jat.4130

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Estrogen Receptor 1 (ESR1) Agonist Induces Ovarian Differentiation and Aberrant Mullerian Duct Development in the Chinese Soft-shelled Turtle, Pelodiscus sinensis2020

    • Author(s)
      Toyota Kenji、Masuda Shoichiro、Sugita Sarina、Miyaoku Kaori、Yamagishi Genki、Akashi Hiroshi、Miyagawa Shinichi
    • Journal Title

      Zoological Studies

      Volume: 59

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression dynamics of genes in the hypothalamic-pituitary-thyroid (HPT) cascade and their responses to 3,3′,5-triiodo-l-thyronine (T3) highlights potential vulnerability to thyroid-disrupting chemicals in zebrafish (Danio rerio) embryo-larvae2020

    • Author(s)
      Parsons Aoife E.、Lange Anke、Hutchinson Thomas H.、Miyagawa Shinichi、Iguchi Taisen、Kudoh Tetsuhiro、Tyler Charles R.
    • Journal Title

      Aquatic Toxicology

      Volume: 225 Pages: 105547-105547

    • DOI

      10.1016/j.aquatox.2020.105547

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hedgehog signaling regulates the basement membrane remodeling during folliculogenesis in the neonatal mouse ovary2020

    • Author(s)
      Terauchi Karin J.、Miyagawa Shinichi、Iguchi Taisen、Sato Tomomi
    • Journal Title

      Cell and Tissue Research

      Volume: 381 Issue: 3 Pages: 555-567

    • DOI

      10.1007/s00441-020-03222-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A newly developed genetic sex marker and its application to understanding chemically induced feminisation in roach (Rutilus rutilus)2020

    • Author(s)
      Lange Anke、Paris Josephine R.、Gharbi Karim、Cezard Timothee、Miyagawa Shinichi、Iguchi Taisen、Studholme David J.、Tyler Charles R.
    • Journal Title

      Molecular Ecology Resources

      Volume: 20 Issue: 4 Pages: 1007-1022

    • DOI

      10.1111/1755-0998.13166

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] マウス外生殖器におけるホルモン環境に依存した性ホルモン受容体の発現2020

    • Author(s)
      佐伯英敏、宮川信一、平野優、梶本みずき、山田源
    • Journal Title

      和歌山医学

      Volume: 70 Pages: 59-65

    • NAID

      40021977367

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research 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 Annual Research 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 Annual Research Report 2018 Annual Research 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 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of hepatic thyroid hormone-responsive genes in neonatal rats: Potential targets for thyroid hormone-disrupting chemicals.2018

    • Author(s)
      Fujimoto N., Kitamura S., Uramaru N., Miyagawa S., Iguchi T.
    • Journal Title

      Toxicology Letters

      Volume: 286 Pages: 48-53

    • DOI

      10.1016/j.toxlet.2018.01.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 温度センサータンパク質TRP及び体温調節行動における温度感受性の相関進化2020

    • Author(s)
      赤司寛志、宮川信一
    • Organizer
      生物環境イノベーション研究部門公開シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 三次元イメージング技術を用いた総排泄腔分割の解析:発生異常メカニズムの解明に向けて2020

    • Author(s)
      松丸大輔、村嶋亜紀、宮川信一、原田理代、山田源、中西剛
    • Organizer
      フォーラム2020:衛生薬学・環境トキシコロジー
    • Related Report
      2020 Annual Research Report
  • [Presentation] 総排泄腔分割の三次元イメージング解析:発生毒性メカニズムの解明に向けて2020

    • Author(s)
      松丸大輔、村嶋亜紀、宮川信一、原田理代、山田源、中西剛
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 温度環境に依存する爬虫類の性決定2019

    • Author(s)
      宮川信一
    • Organizer
      第66回日本生態学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 環境に依存する性と生殖の研究2018

    • Author(s)
      宮川信一
    • Organizer
      日本比較内分泌学会第43回大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Approaches for studying endocrine disruption and estrogen receptors in medaka2018

    • Author(s)
      Miyagawa S, Tohyama S, Ogino Y, Kobayashi T, Lange A, Tyler CR, Iguchi T
    • Organizer
      日本内分泌攪乱化学物質学会第21回研究発表会
    • Related Report
      2018 Annual Research Report
    • Invited

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

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