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Establishment of in vitro oogenesis with high integrity

Planned Research

Project AreaEnsuring integrity in gametogenesis
Project/Area Number 18H05547
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo University of Agriculture

Principal Investigator

Obata Yayoi  東京農業大学, 生命科学部, 教授 (70312907)

Project Period (FY) 2018-06-29 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥110,500,000 (Direct Cost: ¥85,000,000、Indirect Cost: ¥25,500,000)
Fiscal Year 2022: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2021: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2020: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2019: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2018: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Keywords卵子 / 卵子形成過程 / 卵胞形成過程 / 発生能 / in vitro / 卵子形成 / 卵胞形成 / エピジェネティクス
Outline of Final Research Achievements

This study aimed to develop an in vitro system to produce oocytes that achieves high integrity from primordial germ cells. Excessive activation of estrogen signaling in vitro-derived ovaries led to premature expression of AMH, resulting in abnormal follicle formation. On the other hand, the addition of AFP, which is secreted from fetal liver, to the culture medium suppressed estrogen signaling and resulted in normal follicle formation. Furthermore, lowering the concentration of oxygen from 20 to 7% during follicle culture improved abnormal lipid metabolism, restored mitochondrial activity, and improved post-fertilization development in the oocytes. The combination of the improved in vitro system and the exogenous gene transfection was shown to be an effective tool for analyzing the function of genes that work during oogenesis.

Academic Significance and Societal Importance of the Research Achievements

始原生殖細胞(PGC)から卵子を産生するin vitro系の開発は卵子形成機構解明のツールとして有用なばかりでなく、多能生幹細胞から作られる始原生殖細胞様細胞(PGCLC)をもとに成熟卵子を量産させる可能性を秘めている。本研究ではin vitro系を開発する過程で、機能的な成熟卵子の産生に不可欠な卵胞構造の形成に必要な因子が明らかにされた。早発卵巣不全は、世界の40歳未満の女性の1%が罹患しており、女性の不妊症の主要因で早期に卵胞が枯渇することによる。卵胞の形成機構の理解はこうした不妊のメカニズムの解明や治療法の開発に役立つ可能性がある。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (37 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (14 results) (of which Invited: 3 results) Remarks (5 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Harvard Medical School(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Northwest Normal University(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Northwest Normal University(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Harvard Medical School(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Northwest Normal University(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Harvard Medical School(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Disruption of piRNA machinery by deletion of ASZ1/GASZ results in the expression of aberrant chimeric transcripts in gonocytes2022

    • Author(s)
      Ikeda S, Tanaka K, Ohtani R, Kanda A, Sotomaru Y, Kono T, Obata Y.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 68 Issue: 2 Pages: 125-136

    • DOI

      10.1262/jrd.2021-146

    • NAID

      130008145874

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insights into in vivo follicle formation: a review of in vitro systems.2022

    • Author(s)
      Tanimoto R, Yoshida K, Ikeda S, Obata Y.
    • Journal Title

      Histochem Cell Biol.

      Volume: 157 Issue: 3 Pages: 333-345

    • DOI

      10.1007/s00418-021-02058-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimal conditions for mouse follicle culture2021

    • Author(s)
      Ota S, Ikeda S, Takashima T, Obata Y.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 67 Issue: 5 Pages: 327-331

    • DOI

      10.1262/jrd.2021-091

    • NAID

      130008112026

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of in vitro growth on mouse oocyte competency, mitochondria and transcriptome.2021

    • Author(s)
      Takashima T, Fujimaru T, Obata Y.
    • Journal Title

      Reproduction.

      Volume: 162 Issue: 4 Pages: 307-318

    • DOI

      10.1530/rep-21-0209

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oocyte-specific gene knockdown by intronic artificial microRNAs driven by <i>Zp3</i> transcription in mice2021

    • Author(s)
      Sasaki K, Takaoka S, Obata Y
    • Journal Title

      Journal of Reproduction and Development

      Volume: 67 Issue: 3 Pages: 229-234

    • DOI

      10.1262/jrd.2020-146

    • NAID

      130008055064

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blocking estrogen-induced AMH expression is crucial for normal follicle formation2021

    • Author(s)
      Tanimoto Ren、Sekii Kiyono、Morohaku Kanako、Li Jianzhen、Pepin David、Obata Yayoi
    • Journal Title

      Development

      Volume: 148 Issue: 6

    • DOI

      10.1242/dev.197459

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Separation of Follicular Cells and Oocytes in Ovarian Follicles of Zebrafish2021

    • Author(s)
      Wang W, Kang T, Bai L, Hu W, Obata Y, Li J
    • Journal Title

      J Vis Exp

      Volume: 170 Issue: 170

    • DOI

      10.3791/62027

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dnmt3a2/Dnmt3L Overexpression in the Dopaminergic System of Mice Increases Exercise Behavior through Signaling Changes in the Hypothalamus2020

    • Author(s)
      Cui D, Mesaros A, Burdeos G, Voigt I, Giavalisco P, Hinze Y, Purrio M, Neumaier B, Drzezga A, Obata Y, Endepols H, Xu X
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 17 Pages: 6297-6297

    • DOI

      10.3390/ijms21176297

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 哺乳類の卵子を体外で産生する2019

    • Author(s)
      諸白家奈子、尾畑やよい
    • Journal Title

      生物工学会誌

      Volume: 97 Pages: 212-212

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ectopic expression of DNA methyltransferases DNMT3A2 and DNMT3L leads to aberrant hypermethylation and postnatal lethality in mice2019

    • Author(s)
      Sasaki Keisuke、Hara Satoshi、Yamakami Reina、Sato Yusuke、Hasegawa Saki、Kono Tomohiro、Morohaku Kanako、Obata Yayoi
    • Journal Title

      Molecular Reproduction and Development

      Volume: 印刷中 Issue: 6 Pages: 614-623

    • DOI

      10.1002/mrd.23137

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 哺乳動物の卵子を体外で産生する2019

    • Author(s)
      諸白家奈子、尾畑やよい
    • Journal Title

      生物工学会誌

      Volume: 97 Pages: 21-21

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウスHSD3B6欠損が生殖機能に及ぼす影響2022

    • Author(s)
      丸山莉菜、武田ひかり、八木有紀、尾畑やよい
    • Organizer
      第45回日本分子生物学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アデノ随伴ウイルスによるKitl-Sltマウスの卵子形成レスキュー2022

    • Author(s)
      吉田匡汰、木村覚、城本悠助、篠原美都、篠原隆司、尾畑やよい
    • Organizer
      第115回日本繁殖生物学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 生命をつなぐ生殖細胞 ー受精卵ができるまでー2022

    • Author(s)
      尾畑やよい
    • Organizer
      第130回日本畜産学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] マウス体外成長卵母細胞の発生能に影響しうる因子の探査2021

    • Author(s)
      高島友弥、藤丸翼、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Y染色体の存在がマウス雌性生殖系列に及ぼす影響2020

    • Author(s)
      佐藤義治、坂下陽彦、神田暁史、河野友宏、外丸祐介、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス胎仔卵巣培養のための完全合成培地の構築にむけて2020

    • Author(s)
      木村覚、池田晋也、荒井美希、吉田幸太郎、尾畑やよい
    • Organizer
      日本卵子学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 卵母細胞特異的遺伝子ノックダウンシステムの開発2019

    • Author(s)
      佐々木恵亮、尾畑やよい
    • Organizer
      日本分子生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 合成培地におけるin vitroマウス卵子形成2019

    • Author(s)
      木村覚、池田晋也、尾畑やよい
    • Organizer
      日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 卵母細胞特異的ノックダウンシステムの確立2019

    • Author(s)
      佐々木恵亮、高岡沙綾、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] レトロトランスポゾンの脱抑制がマウス前精原細胞の遺伝子発現制御に与える影響2019

    • Author(s)
      池田晋也、田中康貴、大谷麗子、飯田有紀、樋浦仁、外丸祐介、尾畑やよい、河野友宏
    • Organizer
      日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス始原生殖細胞で発現するsmall RNA2018

    • Author(s)
      高島友弥、横田将、樋浦仁、小林久人、尾畑やよい、小川英彦、河野友宏
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 卵子形成を再現するin vitro系の開発2018

    • Author(s)
      尾畑やよい
    • Organizer
      日本生殖免疫学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 体外成長卵母細胞から作出したマウス2細胞期胚のトランスクリプトーム解析2018

    • Author(s)
      藤丸翼、谷本連、小林久人、河野友宏、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 卵胞成長培地に添加するポリビニルピロリドンの分子量が卵の成熟および発生に及ぼす影響2018

    • Author(s)
      尾畑やよい、諸白家奈子、廣江綾香、田口精一
    • Organizer
      日本卵子学会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 「卵子の品質保証機構解明に一歩近づく」Reproduction 最優秀論文賞 受賞

    • URL

      https://www.nodai.ac.jp/news/article/reproduction-2021/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 「卵子の遺伝子機能解析システムを開発」がJRD 最優秀論文賞を受賞

    • URL

      https://www.nodai.ac.jp/news/article/journal-od-reproduction-and-development-2021/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 東京農業大学生命科学部バイオサイエンス学科動物発生工学研究室HP

    • URL

      https://www.nodai.ac.jp/academics/life_sci/bio/lab/505/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 配偶子インテグリティの構築HP

    • URL

      https://www.gamete-integrity.com

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京農業大学HP

    • URL

      https://www.nodai.ac.jp/academics/life_sci/bio/lab/505/

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 品質評価方法及び品質評価プログラム2022

    • Inventor(s)
      八幡穣、野村暢彦、高部響介、尾畑やよい(9番目)、他5名
    • Industrial Property Rights Holder
      筑波大学、東京農業大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-043135
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report

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Published: 2018-07-20   Modified: 2025-01-30  

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