Mechanism of Glycine Receptor Agonist Effect on Embryonic Development and Application to the Prevention of Oocyte Aging

• Project/Area Number: 17K11222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: University of Toyama
• Principal Investigator: Nishizono Hirofumi 富山大学, 学術研究部医学系, 助教 (10502289)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 卵子老化 / グリシンレセプター / 初期発生 / 生殖医学 / アミノ酸受容体

Outline of Final Research Achievements

In this study, we found that the glycine receptor α4 subunit was expressed in mouse fertilized eggs. Also, the inhibition of the glycine receptor α4 subunit function by inhibitors or gene disruption caused embryonic development to stop after the 4-cell stage. Furthermore, we have shown that enhancing glycine receptor function improves the developmental rate of low-developmental-rate fertilized eggs. Thus, we have shown that the glycine receptor α4 subunit is essential for early development.

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで哺乳類では機能が明らかになっていなかったグリシンレセプターα4がマウスの受精卵で発現しており、さらに4細胞期以降の発生に重要であることを示したこと、またその機能亢進により受精率の向上効果が期待できることを示した点で重要である。

Research Products

• [Journal Article] Glycine receptor α4 subunit facilitates the early embryonic development in mice (2020)
  • Author(s): Nishizono Hirofumi、Darwish Mohamed、Endo Takaho A、Uno Kyosuke、Abe Hiroyuki、Yasuda Ryohei
  • Journal Title: Reproduction Volume: 159 Issue: 1 Pages: 41-41
  • DOI: 10.1530/rep-19-0312
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Use of Freeze-thawed Embryos for High-efficiency Production of Genetically Modified Mice (2020)
  • Author(s): Nishizono Hirofumi、Darwish Mohamed、Uosaki Hideki、Masuyama Nanami、Seki Motoaki、Abe Hiroyuki、Yachie Nozomu、Yasuda Ryohei
  • Journal Title: Journal of Visualized Experiments Volume: － Issue: 158 Pages: 1-1
  • DOI: 10.3791/60808
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rapid and high-efficient generation of mutant mice using freeze-thawed embryos of the C57BL/6J strain (2019)
  • Author(s): Darwish Mohamed、Nishizono Hirofumi、Uosaki Hideki、Sawada Hitomi、Sadahiro Taketaro、Ieda Masaki、Takao Keizo
  • Journal Title: Journal of Neuroscience Methods Volume: 317 Pages: 149-156
  • DOI: 10.1016/j.jneumeth.2019.01.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cleavage Speed and Blastomere Number in DBA/2J Compared with C57BL/6J Mouse Embryos (2017)
  • Author(s): Nishizono H, Uno K, Abe H.
  • Journal Title: Journal of the American Association for Laboratory Animal Science Volume: 56 Pages: 11-17
  • Peer Reviewed / Open Access
• [Presentation] Glycine Receptor Α4 Subunit Supports The Early Development Of Mouse Embryos. (2019)
  • Author(s): 西園啓文
  • Organizer: 52nd SSR Annual Conference
  • Int'l Joint Research
• [Presentation] Generation of glycine receptor alpha 4 knockout mice using high-efficient modified CRISPR-Cas9 protocol. (2018)
  • Author(s): Mohamed Darwish
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Generation and Characterization of Glycine Receptor Alpha 4 Knockout Mice. (2018)
  • Author(s): 西園啓文
  • Organizer: 第41回日本神経科学大会
• [Presentation] 分子探索支援により明らかになったグリシンレセプターα4サブユニットの卵子および脳での機能 (2018)
  • Author(s): 西園啓文
  • Organizer: 先端モデル動物支援プラットフォーム・若手支援技術講習会
• [Presentation] Generation of Glycine Receptor Alpha 4 knockout Mice Using High-efficient Modified CRISPR-Cas9 Protocol. (2018)
  • Author(s): Mohamed Darwish
  • Organizer: 先端モデル動物支援プラットフォーム成果発表会