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Investigation of the pathogenesis of imprinting disorders in ART patients and search for risk factors in ART

Research Project

Project/Area Number 18K09215
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionTokyo University of Agriculture (2019-2020)
Tohoku University (2018)

Principal Investigator

HIURA Hitoshi  東京農業大学, 生命科学部, 准教授 (70451523)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords生殖補助医療(ART) / インプリント疾患 / DNAメチル化 / ART / 先天性インプリンティング異常症
Outline of Final Research Achievements

In this study, we compared comprehensive DNA methylation in peripheral blood with assisted reproductive technologies (ART)-conceived and spontaneously conceived imprinting disorders (Silver-Russell syndrome and Beckwith-Wiedemann syndrome) patients to evaluate risk factors for ART. We found that ART-conceived patients had incomplete and more widespread DNA methylation variations (DMVs) than spontaneously conceived patients, especially in sperm-specific methylated regions. These results suggest that the imprinting disorders related to ART might tend to take place just after fertilization at a time when the epigenome is most vulnerable and might be affected by the techniques of manipulation used for in vitro fertilization or intracytoplasmic sperm injection and the culture medium of the fertilized egg.

Academic Significance and Societal Importance of the Research Achievements

晩婚化の社会情勢に伴い、生殖補助医療(ART)が急速に普及してきた。しかし、これまで非常に稀であったゲノムインプリンティング(GI)異常症の発症頻度が増加していることが世界中で報告されている。本研究では、ART由来のGI異常症と非ART由来の患者末梢血のDNAメチル化を比較し、ARTのリスク要因について評価した。その結果、DNAメチル化可変領域はARTにおける体外受精または顕微授精操作、体外培養に用いられる培養液等によって影響される可能性が示唆された。本研究成果はARTにおける疾患発症予防に繋がることが期待できる。

Report

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

    (9 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (4 results) (of which Invited: 3 results) Book (1 results)

  • [Journal Article] Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF42020

    • Author(s)
      Ochiai Kyoko、Yamaoka Mari、Swaminathan Amrutha、Shima Hiroki、Hiura Hitoshi、Matsumoto Mitsuyo、Kurotaki Daisuke、Nakabayashi Jun、Funayama Ryo、Nakayama Keiko、Arima Takahiro、Ikawa Tomokatsu、Tamura Tomohiko、Sciammas Roger、Bouvet Philippe、Kundu Tapas K.、Igarashi Kazuhiko
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 12 Pages: 108517-108517

    • DOI

      10.1016/j.celrep.2020.108517

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Short communication: Menaquinone-4 (vitamin K2) induces proliferation responses in bovine peripheral blood mononuclear cells2020

    • Author(s)
      Bai H.、Hiura H.、Obara Y.、Kawahara M.、Takahashi M.
    • Journal Title

      Journal of Dairy Science

      Volume: 103 Issue: 8 Pages: 7531-7534

    • DOI

      10.3168/jds.2019-17987

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of four imprinting disorders and ART.2019

    • Author(s)
      Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
    • Journal Title

      Clinical Epigenetics

      Volume: 11 Pages: 21-21

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivation of Human Trophoblast Stem Cells.2018

    • Author(s)
      Okae H, Toh H, Sato T, Hiura H, Takahashi S, Shirane K, Kabayama Y, Suyama M, Sasaki H, Arima T.
    • Journal Title

      Cell Stem Cell.

      Volume: 22 Pages: 50-63

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] インプリンティング疾患と生殖補助医療のリスク要因2019

    • Author(s)
      服部裕充、樋浦仁、北村茜、宮内尚子、小林記緒、高橋聡太、岡江寛明、京野廣一、鏡雅代、緒方勤、有馬隆博
    • Organizer
      第14回日本生殖発生医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト胎盤幹(TS)細胞の樹立とその細胞特性2019

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第14回日本生殖発生医学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ヒト胎盤のトロフォブラスト幹細胞の樹立と臨床への応用2018

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ARTによるエピジェネティクスの変調2018

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第63回日本生殖医学会学術講演会・総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] Therapeutic approaches to imprinting diseases. Epigenetics in Human Disease2018

    • Author(s)
      Hattori H, Hiura H, Kobayashi N, Takahashi S, Okae H, Arima T.
    • Total Pages
      6
    • Publisher
      Academic Press.
    • Related Report
      2018 Research-status Report

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

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