The study of the regulation of ovarian development and function by follicular exosome.

• Project/Area Number: 17H03900
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Animal production science
• Research Institution: The University of Tokyo
• Principal Investigator: Sugiura Koji 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (20595623)
• Co-Investigator(Kenkyū-buntansha): 城口 克之 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (00454059) ; 藤井 渉 東京大学, 大学院農学生命科学研究科(農学部), 助教 (40708161)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: エクソソーム / 卵巣 / 繁殖

Outline of Final Research Achievements

This study showed that ovarian follicular exosomes are mainly produced by ovarian mural granulosa cells (MGCs) in mammals. The follicular exosomes are taken-up by ovarian cells to regulate hormonal production and development of oocytes. Normal follicular development requires factors secreted from oocytes, but the oocyte factors show no effects on the exosome release by MGCs. Moreover, we have produced a mouse model for the study of exosome function in ovaries.

Academic Significance and Societal Importance of the Research Achievements

卵巣異常や疾患は動物のメスの繁殖障害の主要因の一つであるが、その発症メカニズムの多くは未だに不明である。本研究では、近年、新たな細胞間コミュニケーション因子として注目されるエクソソームに着目し、卵巣におけるその機能解析を行った。これは哺乳類卵巣の発達や機能制御メカニズムの理解という点で高い学術的意義を有している。さらに、本研究から得られた知見は、エクソソーム異常に起因する卵巣異常・疾患の同定につながることから、畜産など広い分野への応用可能なものである。

Research Products

• [Journal Article] Expression and function of exportin 6 in full-grown and growing porcine oocytes (2019)
  • Author(s): ONUMA Asuka、FUJIOKA Yoshie A.、FUJII Wataru、SUGIURA Koji、NAITO Kunihiko
  • Journal Title: Journal of Reproduction and Development Volume: 65 Issue: 5 Pages: 407-412
  • DOI: 10.1262/jrd.2019-040
  • NAID: 130007732104
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of mRNA profiles of the exosome-like vesicles in porcine follicular fluid (2019)
  • Author(s): Matsuno Yuta、Kanke Takuya、Maruyama Natsumi、Fujii Wataru、Naito Kunihiko、Sugiura Koji
  • Journal Title: PLOS ONE Volume: 14 Issue: 6 Pages: e0217760-e0217760
  • DOI: 10.1371/journal.pone.0217760
  • Peer Reviewed / Open Access
• [Journal Article] Generation of genetically modified mice using SpCas9-NG engineered nuclease (2019)
  • Author(s): Fujii Wataru、Ito Haruka、Kanke Takuya、Ikeda Arisa、Sugiura Koji、Naito Kunihiko
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 12878-12878
  • DOI: 10.1038/s41598-019-49394-5
  • Peer Reviewed / Open Access
• [Journal Article] High-fidelity endonuclease variant HypaCas9 facilitates accurate allele-specific gene modification in mouse zygotes (2019)
  • Author(s): Ikeda Arisa、Fujii Wataru、Sugiura Koji、Naito Kunihiko
  • Journal Title: Communications Biology Volume: 2 Issue: 1 Pages: 371-371
  • DOI: 10.1038/s42003-019-0627-8
  • Peer Reviewed / Open Access
• [Journal Article] Expression of genes involved in the non-neuronal cholinergic system and their possible functions during ovarian follicular development in mice. (2019)
  • Author(s): Ueno M, Ito H, Kanke T, Matsuno Y, Fujii W, Naito K, Sugiura K.
  • Journal Title: J. Mamm. Ova Res. Volume: 35 Pages: 61-69
  • NAID: 40022065358
  • Peer Reviewed
• [Journal Article] Contributions of UBE2C and UBE2S to meiotic progression of porcine oocytes (2018)
  • Author(s): Fujioka YA, Onuma A, Fujii W, Sugiura K, Naito K.
  • Journal Title: Journal of Reproduction and Development Volume: 64 Issue: 3 Pages: 253-259
  • DOI: 10.1262/jrd.2018-006
  • NAID: 130007409956
  • ISSN: 0916-8818, 1348-4400
• [Presentation] A model for studying transdifferentiation of granulosa cells into Sertoli-like cells in mice. (2018)
  • Author(s): Ito H, Kishi K, Emori C, Fujii W, Kanai Y, Naito K, Sugiura K
  • Organizer: 51st Annual meeting of society for the study of reproduction
  • Int'l Joint Research
• [Presentation] Appropriate regulation of Noggin expression in follicles is critical for female fertility in mice. (2018)
  • Author(s): Sugiura K, Emori C, Kogo T, Kanke T, Ito H, Fujii W, Naito K.
  • Organizer: 51st Annual meeting of society for the study of reproduction
• [Presentation] Possibility of transdifferentiating mouse granulosa cells into Sertoli-like cells in vitro. (2017)
  • Author(s): Ito H, Emori C, Fujii W, Naito K, Sugiura K
  • Organizer: 4th World Congress of Reproductive Biology
  • Int'l Joint Research
• [Presentation] Mouse granulosa cells secrete functional extracellular vesicles in vitro (2017)
  • Author(s): Matsuno Y, Fujii W, Natio K, Sugiura K.
  • Organizer: 4th World Congress of Reproductive Biology
  • Int'l Joint Research
• [Presentation] Mouse granulosa cells secrete exosomes independently of oocyte regulation in vitro (2017)
  • Author(s): 松野雄太、Dang Quoc Thuyet、藤井渉、大下誠一、内藤邦彦、杉浦幸二
  • Organizer: 第123回日本畜産学会
• [Presentation] Senescence in ovarian cells (2017)
  • Author(s): 福長一鈴、向後智明、藤井渉、内藤邦彦、杉浦幸二
  • Organizer: 第123回日本畜産学会