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Creation of mammalian oocytes with high fertility by spatiotemporal regulation of the function of mitochondria

Research Project

Project/Area Number 18H02328
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42010:Animal production science-related
Research InstitutionOkayama University

Principal Investigator

FUNAHASHI Hiroaki  岡山大学, 環境生命科学学域, 教授 (50284089)

Co-Investigator(Kenkyū-buntansha) 中塚 幹也  岡山大学, 保健学域, 教授 (40273990)
若井 拓哉  岡山大学, 環境生命科学学域, 准教授 (60557768)
大槻 高史  岡山大学, ヘルスシステム統合科学学域, 教授 (80321735)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords卵母細胞 / 初期発生能 / ミトコンドリア / 時空間的制御 / オートファジー / ミトコンドリアDNA / マイトファジー
Outline of Final Research Achievements

The aim of this study was to generate oocytes with high developmental competence by regulating the mitochondrial (mt) DNA copy number in the ooplasm. Porcine ooplasmic mtDNA copy number did not change during in vitro maturation (IVM) and was lower in oocytes from small than medium follicles. Drp1 (mt mitogen) was reduced during early development, and its inhibition impaired the mt distribution in oocytes and early developmental competence. Overexpression of PGC1alpha (mt synthesis-related genes) resulted in increased reactive oxygen species and mtDNA copy number reduction in oocytes, and reduced IVM rate and early developmental competence. The autophagic potential of oocytes varied greatly during IVM and early development, and differed significantly by follicle diameter of origin. Attempts to introduce photosensitizers and peptide/protein molecular tools into oocytes have not resulted in significant improvement.

Academic Significance and Societal Importance of the Research Achievements

本研究は、卵細胞質のミトコンドリアDNAコピー数制御機構の時空間的調節により発生能の高い卵母細胞作出を目的とした。卵母細胞内でミトコンドリア活性に影響を及ぼすmt分裂因子Drp1の特性やオートファジー能の変動に関する知見は、卵母細胞の初期発生能制御機構の理解に貢献し、発生能や妊孕性の高い卵母細胞作出の基礎的知見として生殖補助医療や動物生産の領域の発展に資する。また、やミトコンドリア合成関連遺伝子(PGC1alpha)の強制発現や光触媒分子ツールの卵細胞室内導入に関する挑戦的知見は、今後の同分野における学術的発展の参考になるものと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (19 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] University of Murcia(スペイン)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Murcia(スペイン)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Relative transcript abundance in porcine cumulus cells collected from different sized follicles2020

    • Author(s)
      Moros‐Nicolas Carla、Izquierdo‐Rico Ma Jose、Li Yang、Gonzalez‐Brusi Leopoldo、Romar Raquel、Funahashi Hiroaki
    • Journal Title

      Reproduction in Domestic Animals

      Volume: 56 Issue: 2 Pages: 374-380

    • DOI

      10.1111/rda.13881

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The autophagic inducer and inhibitor display different activities on the meiotic and developmental competencies of porcine oocytes derived from small and medium follicles2019

    • Author(s)
      Chiyuki KOHATA-ONO, Takuya WAKAI and Hiroaki FUNAHASHI
    • Journal Title

      Journal of Reproduction and Development

      Volume: 65 Issue: 6 Pages: 527-532

    • DOI

      10.1262/jrd.2019-112

    • NAID

      130007768749

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ca2+ signaling and homeostasis in mammalian oocytes and eggs.2019

    • Author(s)
      Wakai T, Mehregan A, Fissore RA
    • Journal Title

      Cold spring harbor perspectives in biology

      Volume: 11 Issue: 12 Pages: a035162-a035162

    • DOI

      10.1101/cshperspect.a035162

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Removal of cumulus cells around 20 h after the start of <i>in vitro</i> maturation improves the meiotic competence of porcine oocytes via reduction in cAMP and cGMP levels2019

    • Author(s)
      Ferre-Pujol, P., Nguyen, X. K., Nagahara, T., Bui, T. T. M., Wakai, T., Funahashi, H.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 65 Issue: 2 Pages: 177-182

    • DOI

      10.1262/jrd.2018-130

    • NAID

      130007630932

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Constitutive IP3R1-mediated Ca2+ release reduces Ca2+ store content and stimulates mitochondrial metabolism in mouse GV oocytes2019

    • Author(s)
      Wakai T, Fissore RA
    • Journal Title

      Journal of Cell Science

      Volume: 132 Issue: 3 Pages: 1-1

    • DOI

      10.1242/jcs.225441

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] XY oocytes of sex-reversed females with a Sry mutation deviate from the normal developmental process beyond the mitotic stage†2018

    • Author(s)
      Sakashita Akihiko、Wakai Takuya、Kawabata Yukiko、Nishimura Chiaki、Sotomaru Yusuke、Alavattam Kris G、Namekawa Satoshi H、Kono Tomohiro
    • Journal Title

      Biology of Reproduction

      Volume: 100 Issue: 3 Pages: 697-710

    • DOI

      10.1093/biolre/ioy214

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ブタ卵母細胞におけるミトコンドリア染色方法の検討2020

    • Author(s)
      門田卓磨・若井拓也・舟橋弘晃
    • Organizer
      第70回関西畜産学会京都大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 体外成熟時のブタ卵母細胞のオートファジー能は由来する小中卵胞で異なる2019

    • Author(s)
      小野千由貴、Mria Serrano Albal, Maria Bobis Rodriguez, 若井拓哉、舟橋弘晃
    • Organizer
      日本卵子学会学術集会第60回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] トレハロースは小卵胞由来ブタ卵母細胞の体外成熟能を改善するがオートファジー能に影響しない2019

    • Author(s)
      小野千由貴、Mria Serrano Albal, Maria Bobis Rodriguez, Laura Cuenca、若井拓哉、舟橋弘晃
    • Organizer
      日本受精着床学会第37回総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 着床前胚発生におけるミトコンドリア分裂因子Drp1の機能解析2019

    • Author(s)
      野村 瑠莉,月向 はるな,舟橋 弘晃,若井 拓哉
    • Organizer
      第60回日本ミトコンドリア学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Trim-Away法を用いたマウス卵母細胞におけるDrp1の機能解析2019

    • Author(s)
      月向 はるな,野村 瑠莉,舟橋 弘晃,若井 拓哉
    • Organizer
      第60回日本ミトコンドリア学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ミトコンドリア分裂因子Drp1の阻害による着床前マウス胚の発生停止2019

    • Author(s)
      野村 瑠莉,月向 はるな,舟橋 弘晃,若井 拓哉
    • Organizer
      第112回日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス卵母細胞におけるTrim-Away法を用いたリン酸化タンパク質の分解2019

    • Author(s)
      月向 はるな,野村 瑠莉,舟橋 弘晃,若井 拓哉
    • Organizer
      第112回日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Animal Biotechnology roles in Livestock Production2019

    • Author(s)
      Hiroaki FUNAHASHI
    • Organizer
      2nd International Conference on Improving Tropical Animal Production for Food Security
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス卵母細胞におけるTrim-away法を用いたDrp1タンパク質の分解2018

    • Author(s)
      月向はるな、野村瑠莉、舟橋 弘晃、若井 拓哉
    • Organizer
      第18回日本ミトコンドリア学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 着床前マウス胚におけるミトコンドリア分裂因子Drp1の役割2018

    • Author(s)
      野村瑠莉、月向はるな、舟橋弘晃、若井拓哉
    • Organizer
      第18回日本ミトコンドリア学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小中卵胞由来ブタ卵母細胞のオートファジー能とVEGFによる助長効果2018

    • Author(s)
      小野千由貴、若井拓哉、舟橋弘晃
    • Organizer
      第36回日本受精着床学会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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