Spermatogonial stem cell niche in seasonal breeding mammals

• Project/Area Number: 15K07688
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Animal production science
• Research Institution: Nihon University
• Principal Investigator: TSUNEKAWA Naoki 日本大学, 生物資源科学部, 教授 (50431838)
• Co-Investigator(Kenkyū-buntansha): 九郎丸 正道 岡山理科大学, 獣医学部, 教授 (00148636) ; 金澤 朋子 日本大学, 生物資源科学部, 助手 (20748470)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 精原幹細胞 / ニッチ / 季節繁殖 / 精子発生 / セルトリ細胞 / 季節繁殖動物 / ハムスター / マウス / セルトリバルブ

Outline of Final Research Achievements

In this study, we identified a valve-like terminal segment of the seminiferous tubules, the Sertoli valve, adjacent to the rete testis as new niche system for GFRalpha1-positive spermatogonia in seasonally breeding hamsters. The Sertoli valve epithelium constitutively expresses GDNF, a major niche factor for SSCs, and supports the stable proliferation and selective maintenance of an A-single subpopulation of GFRalpha1-positive spermatogonia in hamsters. The Sertoli valve region of hamster seminiferous tubules has features that are similar to the stem cell niche in invertebrate gonads. We therefore propose that the Sertoli valve may be a novel niche for A-single GFRalpha1-positive spermatogonia potentially including a SSC population, at the terminal segments of the seminiferous tubules in hamsters.

Academic Significance and Societal Importance of the Research Achievements

種の連綿を支える生殖細胞は、体細胞とは異なる特殊なシステムで制御されている。精子の生産においては、巧妙な細胞分裂様式によって大量生産を可能にしている。その源泉となる細胞が精原幹細胞であり、その細胞が宿る特殊環境をニッチと呼ぶ。本研究課題では、季節によって精巣に大きな変動が認められるハムスターを材料に解析を行ったところ、新たなニッチの発見に至った。これにより、精原幹細胞が局在する新たな領域が明らかとなったことから、精原幹細胞を利用した生殖医療や発生工学的手法による希少動物の保全等、応用利用に必要な基礎的な知見を得た。

Research Products

• [Journal Article] Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice (2017)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay (2016)
  • Author(s): Uchida A, Kishi K, Aiyama Y, Miura K, Takase HM, Suzuki H, Kanai-Azuma M, Iwamori T, Kurohmaru M, Tsunekawa N, Kanai Y
  • Journal Title: Biochem Biophys Res Commun Volume: 476 Issue: 4 Pages: 546-552
  • DOI: 10.1016/j.bbrc.2016.05.160
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Niche for GFRalpha1-Positive Spermatogonia in the Terminal Segments of the Seminiferous Tubules in Hamster Testes (2015)
  • Author(s): Aiyama, Y. Tsunekawa, N. Kishi, K. Kawasumi, M. Suzuki, H. Kanai-Azuma, M. Kurohmaru, M. Kanai, Y.
  • Journal Title: Stem Cells Volume: 33 Issue: 9 Pages: 2811-2824
  • DOI: 10.1002/stem.2065
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] ブタ精巣組織を用いたin vitro精子発生の試み (2018)
  • Author(s): 安田拓央、杉山まどか、金澤朋子、森友忠昭、恒川直樹
  • Organizer: 第161回日本獣医学会学術集会・獣医解剖分科会
• [Remarks] 東京大学獣医解剖学教室
  • URL: http://www.vm.a.u-tokyo.ac.jp/kaibo/