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Challenge of overcoming recurrent IVF failure due to cytoplasmic dysfunction by MST: To secure safety in future generation

Research Project

Project/Area Number 16H05468
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTohoku University

Principal Investigator

TACHIBANA Masahito  東北大学, 大学病院, 講師 (30431571)

Co-Investigator(Kenkyū-buntansha) 志賀 尚美  東北大学, 大学病院, 助教 (20595558)
渡邉 善  東北大学, 大学病院, 助手 (40722567)
井原 基公  東北大学, 医学系研究科, 大学院非常勤講師 (50403506)
黒澤 大樹  東北大学, 医学系研究科, 非常勤講師 (20770192)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywords生殖医学 / 卵細胞質 / 核移植 / 配偶子系列遺伝子治療 / ミトコンドリア
Outline of Final Research Achievements

Aim of this study is to adopt cytoplasmic replacement technique for rescuing cytoplasmic dysfunction in ART. Our initial attempt of MST with mouse oocytes was inefficient due to low fertilization and impaired embryo development. Therefore, we explored and developed a new technique called ProNuclear phase Cytoplasmic Transfer (PNCT). PNCT enables exploit cytoplasm of abnormally fertilized zygote (1PN or 3PN), which normally discarded, and transfer large cytoplast to perivitelline space of 2PN zygotes. PNCT significantly enhanced development of 2PN mouse zygotes to the blastocyst stage and yielded normal pups with confirmed their future fertility.
However, we could not confirm improved embryo development when we applied PNCT to post-ovulatory aged oocytes. We revealed that 1PN cytoplasm was developmentally inferior to 3PN cytoplasm. Thus, we had to restrict to use of 3PN zygote as a source of cytoplast donor for PNCT. Further study will clearly define usefulness of this technique.

Academic Significance and Societal Importance of the Research Achievements

今回開発したPNCT法は廃棄される異常受精胚の細胞質機能に着目した。本法は自己の異常受精胚細胞質を利用する場合、ミトコンドリアのヘテロプラスミーの問題を解決し、配偶子系列の遺伝子改変を伴わない手技となる。一方、他者(若年者)の異常受精胚細胞質を用いる場合でも、廃棄される胚を利用するという点ではより倫理的である。本法は高齢難治性不妊治療における新たな治療戦略を提供する可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Invited: 6 results)

  • [Journal Article] Mitochondrial replacement therapy and assisted reproductive technology: A paradigm shift toward treatment of genetic diseases in gametes or in early embryos2018

    • Author(s)
      Masahito Tachibana, Takashi Kuno and Nobuo Yaegashi
    • Journal Title

      Reproductive Medicine and Biology

      Volume: Oct; 17(4) Issue: 4 Pages: 421-433

    • DOI

      10.1002/rmb2.12230

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 核移植(ミトコンドリア移植)と研究倫理2017

    • Author(s)
      立花眞仁
    • Journal Title

      メディカルエシックス

      Volume: 54 Pages: 41-61

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 成熟卵紡錘体置換(MST)方を用いた配偶子系列遺伝子治療確立へ向けて2017

    • Author(s)
      立花眞仁
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 69(11) Pages: 2241-2251

    • Related Report
      2017 Annual Research Report
  • [Presentation] 核移植が切り開く近未来のART2019

    • Author(s)
      立花眞仁
    • Organizer
      第9回日本・がん生殖医療学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 発生工学研究から派生する生殖補助医療研究と新規治療開発の可能性2019

    • Author(s)
      立花眞仁
    • Organizer
      第19回日本生殖工学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア遺伝病伝搬防止への取り組み~配偶子系列遺伝子治療の幕開け~2018

    • Author(s)
      立花眞仁
    • Organizer
      第59回日本卵子学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 発生工学がつなぐ生殖医療と再生医療2018

    • Author(s)
      立花眞仁
    • Organizer
      第63回日本生殖医学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 前核期細胞質移植による細胞質機能改善の試み2018

    • Author(s)
      藤峯絢子、立花眞仁、久野貴司、東恵子、高橋藍子、田中恵子、井ケ田小緒里、横山絵美、志賀尚美、渡邉善、八重樫伸生
    • Organizer
      第56回東北生殖医学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 配偶子系列遺伝子治療の展望~胚で診断、胚で治す時代は近い?2018

    • Author(s)
      立花眞仁
    • Organizer
      生殖医療技術者のためのリカレントセミナー:仙台セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 成熟卵紡錘体置換(MST)法を用いた配偶子系列遺伝子治療確立へ向けて2017

    • Author(s)
      立花眞仁
    • Organizer
      第69回日本産科婦人科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリア遺伝病に対する核移植を用いた遺伝子治療の試み2017

    • Author(s)
      立花眞仁
    • Organizer
      第9回新生児科指導医教育セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生殖医療とミトコンドリア2017

    • Author(s)
      立花眞仁
    • Organizer
      第31回平成不妊研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリアとPGD/PGS2017

    • Author(s)
      立花眞仁
    • Organizer
      第一回ブラウンテクノロジーズセミナー ART新技術をめぐる展望と課題 PGD/PGSの海外最新知見を考える
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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