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Application of the regulation of endoplasmic reticulum stress to assisted reproductive technology

Research Project

Project/Area Number 18K16790
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionYamagata University

Principal Investigator

Takehara Isao  山形大学, 医学部, 客員研究員 (80642496)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords小胞体ストレス / 加齢卵 / 胚盤胞 / 胚発育 / 妊娠率 / 胚培養 / 胚移植 / 死細胞率 / salubrinal / 卵の質低下
Outline of Final Research Achievements

The age-associated decline in female fertility is largely attributable to a decrease in oocyte quality caused by ovarian aging. In the present study, endoplasmic reticulum stress was strongly associated with aging of post-ovulatory aged mouse oocytes. Salubrinal, an inhibitor of the ER stress-related PERK pathway, significantly improved embryo development of aged mouse oocytes through suppression of blastomeres’ apoptosis. Based on our findings, we propose targeting, ER stress regulation as a new therapeutic strategy to improve oocyte quality.

Academic Significance and Societal Importance of the Research Achievements

高齢女性の不妊治療の治療成績を改善させる治療は全く確立していないのが現状である。今回我々は、小胞体ストレス応答という生体内においてタンパク質の品質を維持する機構が過剰にはたらいてしまうことが卵の加齢による質の低下に関与していることを初めて明らかとした。さらに小胞体ストレス制御薬を使用することで治療成績が改善することをマウスを用いて証明した。この成果により、小胞体ストレス制御が難治性の高齢不妊の治療法に寄与する可能性が示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Impact of endoplasmic reticulum stress on oocyte aging mechanisms2020

    • Author(s)
      Takehara Isao、Igarashi Hideki、Kawagoe Jun、Matsuo Koki、Takahashi Kyoko、Nishi Michi、Nagase Satoru
    • Journal Title

      Molecular Human Reproduction

      Volume: 26 Issue: 8 Pages: 567-575

    • DOI

      10.1093/molehr/gaaa040

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] The regulation of ER stress improved the development of aged oocyte2019

    • Author(s)
      Isao Takehara
    • Organizer
      第75回米国生殖医学会議
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The regulation of endoplasmic reticulum stress improved the development of aged oocytes2018

    • Author(s)
      Isao Takehara
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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