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Application of MSD-AFLP method to explore epigenetic imprints focusing on exposure levels of environmental chemicals

Research Project

Project/Area Number 15H02830
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental impact assessment
Research InstitutionThe University of Tokyo

Principal Investigator

OHSAKO Seiichiroh  東京大学, 大学院医学系研究科(医学部), 准教授 (00274837)

Co-Investigator(Kenkyū-buntansha) 齋藤 俊行  国立研究開発法人量子科学技術研究開発機構, その他部局等, 研究員 (90205667)
Research Collaborator AIBA Toshiki  
HAYASHI Akiko  
SATO Shinji  
YUNOKAWA Harunobu  
FUKAMI Maki  
MIZUNO Kentaro  
HAYASHI Yutaro  
KOJIMA Yoshiyuki  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsDNAメチル化 / 尿道下裂 / 環境汚染物質 / MSD-AFLP / 血液 / 包茎 / 次世代環境影響評価 / 血液DNA / メチル化バイオマーカー / 化学物質
Outline of Final Research Achievements

The prenatal and neonatal exposure to environmental factors such as endocrine disrupting chemicals has been considered to occur epigenetic alterations such as DNA methylation and the changes are persisted in adulthood. Hypospadias, which is reported to be increased in developed countries since the latter half of the last century, has also been suggested to be caused by environmental factors. However, it is still unclear. In this study, we applied the MSD-AFLP, a method for genome-wide DNA methylation profile analysis, to analyze clinical samples of patients with hypospadias and phimosis . As a result, different changes in methylation levels were detected between the hypospadias and the phimosis. The frequency was more pronounced in blood DNA than foreskin DNA. The MSD-AFLP method could be a useful tool to search for disease-specific methylated-CpGs.

Academic Significance and Societal Importance of the Research Achievements

本研究では、胎児期の化学物質曝露により発症が増加することが指摘されている尿道下裂の臨床サンプルを用いて、血液サンプルから病態に特異的なDNAメチル化と思われる変化を検出した。化学物質の曝露が如何にヒトの病態に影響を与えるかを調査する際、従来法では解らなかった曝露の痕跡を見いだせる可能性がある。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (20 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Construction of a High-precision Chemical Prediction System Using Human ESCs2018

    • Author(s)
      山根順子,油谷幸代,今西哲,赤沼宏美,永野麗子,加藤毅,曽根秀子,大迫誠一郎,藤渕航
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 138 Issue: 6 Pages: 815-822

    • DOI

      10.1248/yakushi.17-00213-2

    • NAID

      130007382228

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2018-06-01
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Does the prenatal bisphenol A exposure alter DNA methylation levels in the mouse hippocampus?: An analysis using a high-sensitivity methylome technique2018

    • Author(s)
      Aiba Toshiki、Saito Toshiyuki、Hayashi Akiko、Sato Shinji、Yunokawa Harunobu、Maruyama Toru、Fujibuchi Wataru、Ohsako Seiichiroh
    • Journal Title

      Genes and Environment

      Volume: 40 Issue: 1 Pages: 12-12

    • DOI

      10.1186/s41021-018-0099-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of xenobiotic biomarkers CYP1 family in preputial tissue of patients with hypospadias and phimosis and its association with DNA methylation level of SRD5A2 minimal promoter.2018

    • Author(s)
      Ohsako S, Aiba T, Miyado M, Fukami M, Ogata T, Hayashi Y, Mizuno K and Kojima Y.
    • Journal Title

      Arch Environ Contam Toxicol.

      Volume: 74 Issue: 2 Pages: 240-247

    • DOI

      10.1007/s00244-017-0466-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of dioxin-induced demethylation of mouse Cyp1a1 gene promoter by a new labeling method for short DNA fragments possessing 5'-methylcytosine at the end2018

    • Author(s)
      Kurita Hisaka、Aiba Toshiki、Saito Toshiyuki、Ohsako Seiichiroh
    • Journal Title

      Genes and Environment

      Volume: 40 Issue: 1 Pages: 1-1

    • DOI

      10.1186/s41021-017-0089-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles2017

    • Author(s)
      Aiba Toshiki、Saito Toshiyuki、Hayashi Akiko、Sato Shinji、Yunokawa Harunobu、Maruyama Toru、Fujibuchi Wataru、Kurita Hisaka、Tohyama Chiharu、Ohsako Seiichiroh
    • Journal Title

      BMC Molecular Biology

      Volume: 18 Issue: 1 Pages: 7-7

    • DOI

      10.1186/s12867-017-0083-2

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver.2016

    • Author(s)
      Amenya HZ, Tohyama C, Ohsako S.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34989-34989

    • DOI

      10.1038/srep34989

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells.2016

    • Author(s)
      Yamane J, Aburatani S, Imanishi S, Akanuma H, Nagano R, Kato T, Sone H, Ohsako S, Fujibuchi W.
    • Journal Title

      Nucleic Acids Research

      Volume: 44(12) Issue: 12 Pages: 5515-5528

    • DOI

      10.1093/nar/gkw450

    • NAID

      120005763870

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 男児生殖器異常症とエピゲノム変化:MSD-AFLP法を用いたパイロット研究.2018

    • Author(s)
      相場俊樹、林昭子、齋藤俊行、佐藤伸司、湯野川春信、深見真紀、林祐太郎、水野健太郎、小島祥敬、大迫誠一郎.
    • Organizer
      第89回日本衛生学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低用量ビスフェノールAの胎仔期曝露はマウス海馬のエピゲノムを変化させるかもしれない.2018

    • Author(s)
      大迫誠一郎、栗田尚佳、齋藤俊行、相場俊樹.
    • Organizer
      第18回分子予防環境医学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低用量ビスフェノールAの胎仔期曝露はマウス海馬のエピゲノムを変化させるかもしれない.2018

    • Author(s)
      相場俊樹、栗田尚佳、齋藤俊行、大迫誠一郎.
    • Organizer
      第47回日本環境変異原学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスES細胞を用いた胎児期神経分化モデルにおけるアクリルアミド曝露の影響.2017

    • Author(s)
      若山優里奈、市原学、櫻井敏博、大迫誠一郎.
    • Organizer
      第44回日本毒性学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] MSD-AFLP法の臨床サンプル解析への応用.2017

    • Author(s)
      相場俊樹, 齋藤俊行, 林昭子, 佐藤信治, 湯ノ川春信, 大迫誠一郎.
    • Organizer
      第16回分子予防環境医学研究会
    • Place of Presentation
      熊本市国際会館
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトES細胞を用いた高精度の化合物予測システムの構築.2017

    • Author(s)
      山根順子、油谷幸代、今西哲、赤沼宏美、永野麗子、加藤毅、曽根秀子、大迫誠一郎、藤渕航.
    • Organizer
      日本薬学会第137回年会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] Aryl hydrocarbon receptor drives a robust, dioxin-induced epigenetic modulation of the Cyp1a1 promoter.2016

    • Author(s)
      Hesbon Amanya, Chiharu Tohyama, Seiichiroh Ohsako.
    • Organizer
      第15回分子予防環境医学研究会
    • Place of Presentation
      自治医科大学(栃木県・宇都宮市)
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] 17β-ヒドロキシステロイド脱水素酵素2(Hsd17b2)の胎仔・新生児期生殖器におけるAhr-TCDD依存的誘導性.2016

    • Author(s)
      Mohamed Nassef、Sailendra N Sarma、Hesbon Amenya、相場俊樹、秋田英理奈、呉慶、鈴木純子、福澤徳穂、大迫誠一郎.
    • Organizer
      第15回分子予防環境医学研究会
    • Place of Presentation
      自治医科大学(栃木県・宇都宮市)
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Dioxin induces rapid-onset yet durable epigenetic modulation of the Cyp1a1 promoter.2015

    • Author(s)
      Hesbon Amanya, Chiharu Tohyama, Seiichiroh Ohsako.
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-12-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] DNA Hypomethylation of the Cyp1a1 Promoter Region by Short Term Dioxin Exposure.2015

    • Author(s)
      Hesbon Amanya, Chiharu Tohyama, Seiichiroh Ohsako.
    • Organizer
      第42回日本毒性学会
    • Place of Presentation
      ホテル日航金沢(石川県・金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウスES細胞のダイオキシン曝露におけるin vitro 分化モデルへの影響.2015

    • Author(s)
      佐藤菜乃初、青木札恵、遠山千春、大迫誠一郎.
    • Organizer
      第42回日本毒性学会
    • Place of Presentation
      ホテル日航金沢(石川県・金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Perinatal exposure to dioxins alters the epigenomic program that influences the susceptibility to carcinogens exposed in adulthood.2015

    • Author(s)
      Seiichiroh Ohsako, Hesbon Amenya, Chiharu Tohyama.
    • Organizer
      The 7th International Congress of Asian Society of Toxicology
    • Place of Presentation
      Jeju International Convention Center (韓国、チェジュ市)
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 准教授・大迫誠一郎・ホームページ

    • URL

      http://www.soohsakoss.jp/

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2021-01-27  

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