Ovarian dysfunction related to exosomal deficiency

• Project/Area Number: 20H03124
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42010:Animal production science-related
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2022: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2020: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: エクソソーム / 卵巣 / 卵 / 卵巣疾患

Outline of Research at the Start

動物の卵巣疾患の多くは原因不明であり、家畜繁殖障害や女性不妊症などの予防・治療法開発の障壁となっている。膜小胞エクソソームは、細胞間の情報伝達を担う新規因子として注目されている。エクソソームは卵巣にも存在し、エクソソーム制御異常が未解明の卵巣疾患の原因である可能性がある。本研究では、ブタとマウスをモデルに、エクソソーム欠損に起因する卵巣疾患の同定、卵巣エクソソーム機能の包括的理解、さらにそれを担うエクソソーム内因子を解明する。

Outline of Final Research Achievements

Exosomes contain nucleic acids, proteins, and other substances, and transmit information to target cells. They are also present in ovarian follicles; however, the physiological roles and mechanisms of action of follicular exosomes are not well understood. This study demonstrated that exosomes are taken up by follicular somatic granulosa cells through multiple endocytic pathways, and some of these pathways are influenced by factors secreted by oocytes. Additionally, a novel mouse model was generated, and phenotypic analysis was performed to investigate the physiological functions of follicular exosomes.

Academic Significance and Societal Importance of the Research Achievements

卵巣異常は動物のメスの繁殖障害の主な要因の一つであるが、その発症メカニズムの多くはいまだに理解されていない。本研究では、近年、新たな細胞間情報伝達因子として注目されているエクソソームに着目し、その作用機序の解明や、さらなる解析のためのモデル動物の作製を行った。これは哺乳類卵巣の発達・機能制御メカニズムの理解という学術的意義の高さだけではなく、エクソソーム異常に起因する卵巣異常の同定、診断・治療方法の開発などにつながる社会的意義の高いものである。

Research Products

• [Journal Article] Cooperative effects of oocytes and estrogen on the forkhead box L2 expression in mural granulosa cells in mice (2022)
  • Author(s): Ito Haruka、Emori Chihiro、Kobayashi Mei、Maruyama Natsumi、Fujii Wataru、Naito Kunihiko、Sugiura Koji
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 20158-20158
  • DOI: 10.1038/s41598-022-24680-x
  • Peer Reviewed / Open Access
• [Journal Article] Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro (2022)
  • Author(s): Kanke Takuya、Fujii Wataru、Naito Kunihiko、Sugiura Koji
  • Journal Title: Molecular Reproduction and Development Volume: 89 Issue: 7 Pages: 281-289
  • DOI: 10.1002/mrd.23616
  • Peer Reviewed
• [Journal Article] Expression and regulation of estrogen receptor 2 and its coregulators in mouse granulosa cells (2022)
  • Author(s): EMORI Chihiro, KANKE Takuya, ITO Haruka, AKIMOTO Yuki, FUJII Wataru, NAITO Kunihiko, SUGIURA Koji
  • Journal Title: Journal of Reproduction and Development Volume: 68 Issue: 2 Pages: 137-143
  • DOI: 10.1262/jrd.2021-114
  • NAID: 130008142259
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] 卵分泌因子による卵巣顆粒膜細胞の分化制御機構 (2021)
  • Author(s): 伊藤遥，杉浦幸二
  • Journal Title: Journal of Mammalian Ova Research Volume: 38 Pages: 31-38
  • Peer Reviewed
• [Journal Article] Effects of oocyte‐derived paracrine factors on release of extracellular vesicles by murine mural granulosa cells in vitro (2020)
  • Author(s): Matsuno Yuta、Maruyama Natsumi、Fujii Wataru、Naito Kunihiko、Sugiura Koji
  • Journal Title: Animal Science Journal Volume: 91 Issue: 1
  • DOI: 10.1111/asj.13385
  • Peer Reviewed
• [Journal Article] Oocytes suppress FOXL2 expression in cumulus cells in mice† (2020)
  • Author(s): Emori Chihiro、Ito Haruka、Fujii Wataru、Naito Kunihiko、Sugiura Koji
  • Journal Title: Biology of Reproduction Volume: 103 Issue: 1 Pages: 85-93
  • DOI: 10.1093/biolre/ioaa054
  • Peer Reviewed / Open Access
• [Presentation] 胞状卵胞発達を支える細胞間コミュニケーション (2022)
  • Author(s): 杉浦幸二
  • Organizer: 第63回日本卵子学会学術集会
  • Invited
• [Presentation] ALK5-SMAD2/3 signaling in granulosa cells is required for the acquisition of the oocyte developmental competence (2021)
  • Author(s): Akimoto Y, Fujii W, Naito K, Sugiura K.
  • Organizer: 54th Annual meeting of society for the study of reproduction
  • Int'l Joint Research
• [Presentation] Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro. (2021)
  • Author(s): Kanke T, Fujii W, Naito K, Sugiura K.
  • Organizer: 54th Annual meeting of society for the study of reproduction
  • Int'l Joint Research
• [Presentation] Senescent cells accumulate in ovarian stromal region of aged mice. (2021)
  • Author(s): Maruyama N, Fukunaga I, Kogo T, Fujii W, Naito K, Sugiura K.
  • Organizer: 54th Annual meeting of society for the study of reproduction
  • Int'l Joint Research