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Molecular characterization of mouse gonadal supporting cell lineages in a partial sex reversal

Research Project

Project/Area Number 17H01501
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Animal production science
Research InstitutionThe University of Tokyo

Principal Investigator

Kanai Yoshiakira  東京大学, 大学院農学生命科学研究科(農学部), 教授 (30260326)

Co-Investigator(Kenkyū-buntansha) 平松 竜司  東京大学, 大学院農学生命科学研究科(農学部), 助教 (70555284)
平手 良和  東京医科歯科大学, 統合研究機構, 講師 (70342839)
九郎丸 正道  岡山理科大学, 獣医学部, 教授 (00148636)
高瀬 比菜子  東京医科歯科大学, 大学院医歯学総合研究科, テニュアトラック助教 (40754528)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2019: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2018: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2017: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Keywords支持細胞 / 性的2型 / heterogeneity / 性転換 / 卵精巣 / 性決定 / 哺乳動物 / heterogenity / 性分化 / セルトリ細胞 / 顆粒膜細胞 / テストステロン / AMH / マウス
Outline of Final Research Achievements

In mammals, sex differentiation is initially induced in the gonadal supporting cell lineages which include two minor subpopulations with intersexual states in the dorsal or ventral edges of the developing gonads. In this project, we have characterized the molecular basis of their heterogeneity and the transcriptome alterations during the sexual reversal processes in them. Here, we demonstrate that, by using two sex-reversal model systems, both FGF9 and testosterone contribute to the ectopic appearance of XX Sertoli cells in the ventral edge of the ovary, in addition to their induction of ectopic XY granulosa cells in the dorsal surface area of the testes.

Academic Significance and Societal Importance of the Research Achievements

哺乳動物の睾丸、卵巣の組織中に、性的に未分化性を維持した特殊な支持細胞が存在し、 外からのFGF シグナルとテストステロンの作用によりこの細胞の性が逆転することと、この特殊な支持細胞の分子基盤の特徴の一端を解明したことに学術的な意義がある。ごく一部の特殊な支持細胞の性の揺らぎが、ヒト早期卵巣不全、牛フリーマーチン症などの不妊症の引き金となり得ることから、この細胞を標的とした新たな不妊症の治療、予防法の開発につなげられるものと考えられる。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (32 results)

All 2022 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (4 results) Remarks (3 results)

  • [Int'l Joint Research] University of Utah, School of Medicine(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Queensland(オーストラリア)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules2021

    • Author(s)
      Imura-Kishi Kasane、Uchida Aya、Tsunekawa Naoki、Suzuki Hitomi、Takase Hinako M.、Hirate Yoshikazu、Kanai-Azuma Masami、Hiramatsu Ryuji、Kurohmaru Masamichi、Kanai Yoshiakira
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1110-1110

    • DOI

      10.1038/s41598-020-79987-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode2021

    • Author(s)
      Yamada R, Oguri A, Fujiki K, Shirahige K, Hirate Y, Kanai-Azuma M, Takezoe H, Akimoto Y, Takahashi N, Kanai Y.
    • Journal Title

      Dis Model Mech

      Volume: 14 Issue: 12

    • DOI

      10.1242/dmm.049251

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-cell transcriptional analysis reveals developmental stage-dependent changes in retinal progenitors in the murine early optic vesicle2021

    • Author(s)
      Yamada R, Oguri A, Fujiki K, Shirahige K, Takezoe H, Takahashi N, Kanai Y.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 543 Pages: 80-86

    • DOI

      10.1016/j.bbrc.2021.01.043

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression and functional abnormalities in XX/Sry Leydig cells2021

    • Author(s)
      Yanai Shogo、Baba Takashi、Inui Kai、Miyabayashi Kanako、Han Soyun、Inoue Miki、Takahashi Fumiya、Kanai Yoshiakira、Ohkawa Yasuyuki、Choi Man Ho、Morohashi Ken-ichirou
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 719-719

    • DOI

      10.1038/s41598-020-80741-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Early Crypt Formation Defects in the Uterine Epithelia of Sox17 Heterozygous Mice2021

    • Author(s)
      Hirate Yoshikazu、Hayakawa Kana、Nakano Yuki、Kumazawa Shiori、Miura Kento、Kanai Yoshiakira、Kanai-Azuma Masami
    • Journal Title

      Sexual Development

      Volume: N/A Issue: 1-6 Pages: 1-11

    • DOI

      10.1159/000513386

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular and genetic characterization of partial masculinization in embryonic ovaries grafted into male nude mice.Molecular and genetic characterization of partial masculinization in embryonic ovaries grafted into male nude mice.2019

    • Author(s)
      Miura K, Harikae K, Nakaguchi M, Imaimatsu K, Hiramatsu R, Tomita A, Hirate Y, Kanai-Azuma M, Kurohmaru M, Ogura A, Kanai Y.
    • Journal Title

      PLos One

      Volume: 14(3) Issue: 3 Pages: e0212367-e0212367

    • DOI

      10.1371/journal.pone.0212367

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nr5a1 suppression during the fetal period optimizes ovarian development by fine-tuning of Notch signaling2019

    • Author(s)
      Nomura R, Kashimada K, Suzuki H, Zhao L, Hosokawa-Tsuji A, Yagita H, Takagi M, Kanai Y, Bowles J, Koopman P, Kanai-Azuma M, Morio T.
    • Journal Title

      J Cell Sci

      Volume: 32 Issue: 8

    • DOI

      10.1242/jcs.223768

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche2019

    • Author(s)
      Kitadate Y., Jorg DJ., Tokue M,. Maruyama A., Ishikawa R., Tsuchiya S., Segi-Nishida E., Nakagawa T., Uchida A., Kimura-Yoshida C., Mizuno S., Sugiyama F., Azami T., Ema M., Noda C., Kobayashi S., Matsuo I., Kanai Y., Nagasawa T., Sugimoto Y., Takahashi S., Simons BD., Yoshida S.
    • Journal Title

      Cell Stem Cell

      Volume: 24 Issue: 1 Pages: 79-92

    • DOI

      10.1016/j.stem.2018.11.013

    • NAID

      120007128265

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sox17 is essential for proper formation of the marginal zone of extraembryonic endoderm adjacent to a developing mouse placental disk.2018

    • Author(s)
      Igarashi H, Uemura, M, Hiramatsu R, Hiramatsu R, Segami S, Pattarapanawan M, Hirate Y, Yoshimura Y, Hashimoto H, Higashiyama H, Sumitomo H, Kurohmaru M, Saijoh Y, Suemizu H, Kanai-Azuma M, Kanai Y.
    • Journal Title

      Biol Reprod

      Volume: - Issue: 3 Pages: 578-589

    • DOI

      10.1093/biolre/ioy079

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-mediated knock-in of the murine Y chromosomal <i>Sry</i> gene2018

    • Author(s)
      Imaimatsu K, Fujii W, Hiramatsu R, Miura K, Kurohmaru M, Kanai Y.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 64 Issue: 3 Pages: 283-287

    • DOI

      10.1262/jrd.2017-161

    • NAID

      130007409955

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CRISPR/Cas9-mediated knock-in of murine Y chromosomal Sry gene.2018

    • Author(s)
      Imaimatsu K, Fujii W, Hiramatsu R, Miura K, Kurohmaru M, Kanai Y.
    • Journal Title

      J Reprod Develop

      Volume: 印刷中

    • NAID

      130007409955

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Differentiation of ovaries.2018

    • Author(s)
      Takase MH, Kanai-Azuma M, Kanai Y
    • Journal Title

      Reference Module in Biomedical Sciences

      Pages: 1-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sex determination and differentiation in mammals.2018

    • Author(s)
      Miura K, Tomita Y, Kanai Y
    • Journal Title

      Reproductive & Developmental Strategies: the Continuity of Life

      Pages: 407-433

    • DOI

      10.1007/978-4-431-56609-0_20

    • ISBN
      9784431566076, 9784431566090
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defects in the first wave of folliculogenesis in mouse XO ovaries2017

    • Author(s)
      Kento Miura, Chiharu Murata, Kyoko Harikae, Hitomi Suzuki, Masami Kanai-Azuma, Masamichi Kurohmaru, Naoki Tsunekawa & Yoshiakira Kanai
    • Journal Title

      Journal of Reproduction and Development

      Volume: 63 Issue: 3 Pages: 333-338

    • DOI

      10.1262/jrd.2017-033

    • NAID

      130006362665

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice2017

    • Author(s)
      Kishi Kasane、Uchida Aya、Takase Hinako M、Suzuki Hitomi、Kurohmaru Masamichi、Tsunekawa Naoki、Kanai-Azuma Masami、Wood Stephen A、Kanai Yoshiakira
    • Journal Title

      Reproduction

      Volume: 154 Issue: 2 Pages: 135-143

    • DOI

      10.1530/rep-17-0184

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 頭部外胚葉におけるレンズ誘導におけるMab21l1の機能2021

    • Author(s)
      山田竜一、小栗晶、藤木克則、白髭克彦、平手良和、金井正美、竹添裕高、秋元義弘、高橋直樹、金井克晃.
    • Organizer
      第44回日本分子生物学会年会. 2021年12月1-3日 (ハイブリッド開催, パシフィコ横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス胎子期精巣の性転換系における卵巣化メカニズムの解析.2020

    • Author(s)
      今井松 健也、板橋 寛嗣、冨田 絢子、平松 竜司、金井 克晃.
    • Organizer
      第163回日本獣医学会学術集会. 2020年9月14-30日  (オンライン開催 山口大学)
    • Related Report
      2019 Annual Research Report
  • [Presentation] A single-cell transcriptional analysis reveals developmental stage-dependent changes in retinal progenitors in the murine early optic vesicle.2020

    • Author(s)
      山田竜一、小栗晶、藤木克則、白髭克彦、竹添裕高、高橋直樹、金井克晃
    • Organizer
      第163回日本獣医学会学術集会. 2020年9月14-30日 (オンライン開催 山口大学)
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス胎子期精巣における新規性転換系の樹立とその卵巣化メカニズムの解析.2020

    • Author(s)
      今井松 健也,板橋 寛嗣,冨田 絢子,平松 竜司,金井 克晃.
    • Organizer
      第113回日本繁殖生物学会大会2020年9月23-25日 (オンライン開催 東北大学)
    • Related Report
      2019 Annual Research Report
  • [Presentation] A single-cell transcriptional analysis of early optic vesicle patterning in the developing mouse eye.2020

    • Author(s)
      山田竜一、金井克晃、高橋直樹.
    • Organizer
      第20回東京大学生命科学シンポジウ.2020年10月30-31日 (オンライン開催, 東京大学)
    • Related Report
      2019 Annual Research Report
  • [Presentation] High-FGF9/low-retinoic acid signaling states in Sertoli valve niche for spermatogenic stem/progenitor cells.2018

    • Author(s)
      Yoshiakira Kanai
    • Organizer
      8th International Symposium on vertebrate sex determination. Kona Hawaii, April 16 - 20, 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Amh欠損雄マウスを用いたミューラー管遺残症における遺残子宮の比較病態解析 ワークショップ「脊椎動物の性決定、性分化の分子機構」2018

    • Author(s)
      平松竜司、村田千晴、三浦健人、平手良和、金井正美、金井克晃
    • Organizer
      第41回日本分子生物学会年会 パシフィコ横浜 2018年11月29日
    • Related Report
      2018 Annual Research Report
  • [Presentation] A Niche for GFRα1-Positive Spermatogonia in the Terminal Segments of the Seminiferous Tubules in Mammalian Testes.2017

    • Author(s)
      Kanai Y.
    • Organizer
      he International Research Symposium on Regulation of Germ Cell Development in vivo and in vitro.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 遺伝学の百科事典2022

    • Author(s)
      金井克晃(分担執筆)
    • Total Pages
      690
    • Publisher
      丸善出版
    • ISBN
      9784621306604
    • Related Report
      2019 Annual Research Report
  • [Book] 「遺伝子から解き明かす「性」の不思議な世界」田中実編 (分担執筆, 第6章 哺乳類の生殖腺の性)2019

    • Author(s)
      金井克晃、平松竜司
    • Total Pages
      541
    • Publisher
      一色出版
    • ISBN
      9784909383068
    • Related Report
      2018 Annual Research Report
  • [Book] 獣医発生学 第2版 T. A. McGeady 他著 木曾監修 (担当:共訳)2019

    • Author(s)
      金井克晃、金井正美
    • Total Pages
      434
    • Publisher
      学窓社
    • ISBN
      9784873627632
    • Related Report
      2018 Annual Research Report
  • [Book] Reproductive and Developmental Strategies. Editors: Kobayashi et al. (Eds.) (分担執筆, Chapter 20: Sex determination and differentiation in mammals.)2018

    • Author(s)
      Kento Miura, Ayako Tomita, Yoshiakira Kanai
    • Total Pages
      789
    • Publisher
      Springer, Tokyo.
    • ISBN
      9784431566090
    • Related Report
      2018 Annual Research Report
  • [Remarks] マウス生殖細胞/生殖腺の発生、性分化および精子発生の分子機構の解明

    • URL

      http://www.vm.a.u-tokyo.ac.jp/kaibo/seibunnka.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究紹介・マウス生殖細胞/生殖腺の発生、性分化および精子発生の分子機構の解明

    • URL

      http://www.vm.a.u-tokyo.ac.jp/kaibo/seibunnka.html#miura

    • Related Report
      2018 Annual Research Report
  • [Remarks] 研究紹介・マウス生殖細胞/生殖腺の発生、性分化および精子発生の分子機構の解明

    • URL

      http://www.vm.a.u-tokyo.ac.jp/kaibo/seibunnka.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2024-12-25  

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