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Study for the molecular mechanism in an oocyte aging

Research Project

Project/Area Number 26293364
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Akutsu Hidenori  国立研究開発法人国立成育医療研究センター, その他部局等, その他 (50347225)

Co-Investigator(Kenkyū-buntansha) 菅沼 亮太  福島県立医科大学, 医学部, 講師 (30528211)
浜谷 敏生  慶應義塾大学, 医学部, 講師 (60265882)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords生殖医学 / 受精卵 / 不育症 / 女性医学 / 卵子 / X染色体 / 卵子加齢 / 老化 / 成熟 / β-Catenin
Outline of Final Research Achievements

An oocyte aging is strongly related with impairing totipotency of zygote and X-chromosome inactivation of female embryos is partially key molecule feature on acquiring totipotency. We aimed to explore molecular mechanism on X-chromosome inactivation process in preimplantation development using mice model. An our first accomplishment showed that histone 3 lysine 9 tri-methylation (H3K9me3) was involved in Xm (maternal X-chromosome)-Xist derepression from early preimplantation phases. We also found that the chromatin state at the Xist genomic locus became markedly condensed as oocyte growth proceeded. Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued paternal Xist mutational lethality, indicating that loss of Xm-Xist imprinting was irreversible. We propose that chromatin condensation and fine-tuning of Rnf12 dosage are crucial for Xist imprint maintenance by silencing Xm-Xist (Fukda, et al. Plos genetics 2016).

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 9 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results)

  • [Journal Article] Maintenance of Xist imprinting depends on chromatin condensation state and Rnf12 dosage in mice.2016

    • Author(s)
      Fukuda, A., Mitani, A., Miyashita, T., Sado, T., Umezawa, A., and *Akutsu, H.
    • Journal Title

      PloS Genet.

      Volume: 12(10) Issue: 10 Pages: e1006375-e1006375

    • DOI

      10.1371/journal.pgen.1006375

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice2016

    • Author(s)
      Fukuda A, Mitani A, Miyashita T, Kobayashi H, Umezawa A, Akutsu H
    • Journal Title

      Reproduction

      Volume: 152 Issue: 5 Pages: 417-30

    • DOI

      10.1530/rep-16-0277

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chromatin condensation of Xist genomic loci during oogenesis in mice2015

    • Author(s)
      Fukuda, A., Mitani, A., Miyashita, T., Umezawa, A., Akutsu, H
    • Journal Title

      Development

      Volume: 142 Pages: 4049-4055

    • DOI

      10.1242/dev.127308

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ethical acceptability of research on human-animal chimeric embryos: summary of opinions by the Japanese Expert Panel on Bioethics2015

    • Author(s)
      Mizuno H, Akutsu H, Kato K
    • Journal Title

      Life Sci Soc Policy.

      Volume: 11 Issue: 1 Pages: 15-15

    • DOI

      10.1186/s40504-015-0033-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of primitive neural stem cells from human fibroblasts using a defined set of factors.2015

    • Author(s)
      3.Miura T, Sugawara T, Fukuda A, Machida M, Tamoto R, Kawasaki T, Umezawa A, Akutsu H.
    • Journal Title

      Biology Open

      Volume: 4 Issue: 11 Pages: 1595-1607

    • DOI

      10.1242/bio.013151

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes2015

    • Author(s)
      Atsushi Fukuda, Motohiko Tanino, Ryo Matoba, Akihiro Umezawa, Hidenori Akutsu
    • Journal Title

      Scientific reports

      Volume: 5 Issue: 1 Pages: 14101-14101

    • DOI

      10.1038/srep14101

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Xenogeneic-free defined conditions for derivation and expansion of human embryonic stem cells with mesenchymal stem cells.2015

    • Author(s)
      2.Akutsu H, Machida M, Kanzaki S, Sugawara T, Ohkura T, Nakamura N, Yamazaki-Inoue M, Miura T, Vemuri MC, Rao MS, Miyado K, Umezawa A.
    • Journal Title

      Regenerative Therapy

      Volume: 1 Pages: 18-29

    • DOI

      10.1016/j.reth.2014.12.004

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Notch inhibition allows oncogene-independent generation of iPS cells2015

    • Author(s)
      Ichida JK, T C W J, Williams LA, Carter AC, Shi Y, Moura MT, Ziller M, Singh S, Amabile G, Bock C, Umezawa A, Rubin LL, Bradner JE, Akutsu H, Meissner A, Eggan K
    • Journal Title

      Nature Chemical Biology

      Volume: 1 Issue: 8 Pages: 632-639

    • DOI

      10.1038/nchembio.1552

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice.2014

    • Author(s)
      Fukuda A, Tomikawa J, Miura T, Hata K, Nakabayashi K, Eggan K, Akutsu H, Umezawa A.
    • Journal Title

      Nat Commun.

      Volume: 5 Issue: 1 Pages: 5464-5464

    • DOI

      10.1038/ncomms6464

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 雌性胚の受精卵から個体発生に至るクロマチン制御機構2017

    • Author(s)
      阿久津英憲
    • Organizer
      日本生殖再生医学会 第12回学術集会
    • Place of Presentation
      東京シェーンバッハサボ-
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 多角的ゲノム解析からみる卵子の質評価の可能性2016

    • Author(s)
      阿久津英憲
    • Organizer
      第57回日本卵子学会
    • Place of Presentation
      新潟コンベンションセンター
    • Year and Date
      2016-05-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ES細胞、iPS細胞等を用いる神経難病児者への治療法開発の展望2015

    • Author(s)
      阿久津英憲
    • Organizer
      第二十回日本難病看護学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] The role of asymmetric histone modifications in embryo development2015

    • Author(s)
      Akutsu, Hidenori
    • Organizer
      IFFS/JSRM International Meeting 2015
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生殖医学における ES 細胞とiPS 細胞の意義2014

    • Author(s)
      阿久津英憲
    • Organizer
      第59回日本生殖医学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ヒトES細胞2014

    • Author(s)
      阿久津英憲
    • Organizer
      第26回日本生命倫理学会年次大会
    • Place of Presentation
      浜松
    • Year and Date
      2014-10-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Human induced plurippotent stem cells for disease modeling2014

    • Author(s)
      Hidenori AKUTSU
    • Organizer
      8th International Symposium of Rare DiseaseResearch
    • Place of Presentation
      韓国ソウル
    • Year and Date
      2014-09-18 – 2014-09-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 卵子老化機序解明に向けた ES細胞の応用2014

    • Author(s)
      阿久津英憲
    • Organizer
      第32回日本受精着床学会総会・学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-31 – 2014-08-01
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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