• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Epigenetic mutation induced by environmental factors: a molecular mechanism elucidation of the DOHaD

Research Project

Project/Area Number 23310044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionThe University of Tokyo

Principal Investigator

OHSAKO Seiichiroh  東京大学, 医学(系)研究科(研究院), 准教授 (00274837)

Co-Investigator(Kenkyū-buntansha) TOSHIYUKI Saito  国立研究開発法人放射線医学総合研究所, 重粒子医学センター, 主任研究員 (90205667)
Co-Investigator(Renkei-kenkyūsha) TAKEDA Makio  一般財団法人残留農薬研究所, 毒性部, 室長
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywordsエピジェネティクス / 化学物質 / DOHaD / 環境汚染物質 / ダイオキシン / メチル化 / 発がん / P450
Outline of Final Research Achievements

An attempt of elucidation of molecular mechanism of the DOHaD in which fetal environmental factors are hypothesized to cause an epigenomic alteration and memory persisted in adulthood. Additionally we developed a new genome-wide methylation analysis (MSD-AFLP method). The Cyp1a1 promoter of the liver is hypomethylated from day 3 after birth when given TCDD to pregnant mice and the altered methylation level is maintained until after maturity. Because the Dnmt3b dissociation was found by ChIP assay, we assumed mechanistic possibility of passive demethylation. Whereas we tested whether this memory could happen in the adulthood. In the mouse liver of 10 weeks of age, it was found that hypomethylation was caused by the early point in time such as 24 hours after TCDD administration, suggesting that active demethylation should be considered.

Report

(4 results)
  • 2014 Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (19 results)

All 2014 2013 2012 2011

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (9 results)

  • [Journal Article] A mouse strain less responsive to dioxin-induced prostaglandin E2 synthesis is resistant to the onset of neonatal hydronephrosis.2014

    • Author(s)
      Aida-Yasuoka K, Yoshioka W, Kawaguchi T, Ohsako S, Tohyama C.
    • Journal Title

      Toxicol Sci

      Volume: 141 Issue: 2 Pages: 465-474

    • DOI

      10.1093/toxsci/kfu142

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of amino acid residues in the ligand-binding domain of the aryl hydrocarbon receptor causing the species-specific response to omeprazole: possible determinants for binding putative endogenous ligands.2014

    • Author(s)
      Shiizaki K, Ohsako S, Kawanishi M, and Yagi T.
    • Journal Title

      Mol Pharmacol

      Volume: 85 Pages: 279-289

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single administration of butylparaben induces spermatogenic cell apoptosis in prepubertal rats.2014

    • Author(s)
      Alam MS, Ohsako S, Kanai Y, and Kurohmaru M.
    • Journal Title

      Acta Histochemical

      Volume: 116 Issue: 3 Pages: 474-480

    • DOI

      10.1016/j.acthis.2013.10.006

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates dysregulation of the lipid metabolism in mouse offspring fed a high-calorie diet.2014

    • Author(s)
      Sugai E, Yoshioka W, Kakeyama M, Ohsako S. Tohyama C.
    • Journal Title

      J Appl Toxicol

      Volume: 34 Issue: 3 Pages: 296-306

    • DOI

      10.1002/jat.2881

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prenatal zinc deficiency-dependent epigenetic alterations of mouse metallothionein-2 gene.2013

    • Author(s)
      Kurita H, Ohsako S, Yoshinaga J, Hashimoto S, and Tohyama C.
    • Journal Title

      J Nutr Biochem

      Volume: 24 Issue: 1 Pages: 256-266

    • DOI

      10.1016/j.jnutbio.2012.05.013

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of low-dose thalidomide on dopaminergic neuronal differentiation of human neural progenitor cells: a combined study of metabolomics and morphological analysis2012

    • Author(s)
      Qin XY, Akanuma H, Wei F, Nagano R, Zeng Q, Imanishi S, Ohsako S, Yoshinaga J, Yonemoto J, Tanokura M, Sone H
    • Journal Title

      Neurotoxicology

      Volume: 33 Issue: 5 Pages: 1375-1380

    • DOI

      10.1016/j.neuro.2012.08.016

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of methylmercury exposure on neuronal differentiation of mouse and human embryonic stem cells.2012

    • Author(s)
      He X, Imanishi S, Sone H, Nagano R, Qin X-Y, Yoshinaga J, Akanuma H, Yamane J, Fujibuchi W, and Ohsako S.
    • Journal Title

      Toxicol Lett

      Volume: 212 Issue: 1 Pages: 1-10

    • DOI

      10.1016/j.toxlet.2012.04.011

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice2012

    • Author(s)
      Yoshioka W, Aida-Yasuoka K, Fujisawa N, Kawaguchi T, Ohsako S, Hara S, Uematsu S, Akira S, Tohyama C
    • Journal Title

      Toxicol. Sci

      Volume: 127(2) Issue: 2 Pages: 547-554

    • DOI

      10.1093/toxsci/kfs115

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-parametric profiling network based on gene expression and phenotype data : A novel approach to developmental neurotoxicity testing2012

    • Author(s)
      Nagano R., Akanuma H., Qin X-Y., Imanishi S., Toyoshiba H., Yoshinaga J., Ohsako S., Sone H.
    • Journal Title

      International Journal of Molecular Science

      Volume: 13 Issue: 1 Pages: 187-207

    • DOI

      10.3390/ijms13010187

    • NAID

      130005009157

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perinatal Exposure to Environmental Chemicals Induces Epigenomic Changes in Offspring2011

    • Author(s)
      Ohsako S
    • Journal Title

      Genes and Environment

      Volume: 33 Issue: 2 Pages: 43-49

    • DOI

      10.3123/jemsge.33.43

    • NAID

      10028110787

    • ISSN
      1880-7046, 1880-7062
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Dopaminergic neuronal differentiation visualized by human embryonic stem cell-line carrying rat tyrosine hydroxylase-EGFP transgene.2014

    • Author(s)
      Sailendra Nath SARMA, Masanobu KOHDA, Seiichiroh OHSAKO
    • Organizer
      第42回日本毒性学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2014-07-04
    • Related Report
      2013 Annual Research Report
  • [Presentation] Establishment of a unique profiling method for DNA methylation frequency and its application to toxicology.2014

    • Author(s)
      Aiba Toshiki, Saito Toshiyuki, Hayashi Akiko, Sato Shinji, Yunokawa Harunobu, Kurita Hisaka, Maruyama Toru, Fujibuchi Wataru, Tohyama Chiharu, Ohsako Seiichiroh
    • Organizer
      SOT2014
    • Place of Presentation
      Phoenix, Arizona (U.S.A.)
    • Year and Date
      2014-03-27
    • Related Report
      2013 Annual Research Report
  • [Presentation] MSD-AFLP法の開発とその応用2014

    • Author(s)
      相場俊樹、齋藤俊行、佐藤信治、湯ノ川春信、栗田尚佳、丸山徹、藤渕航、遠山千春、大迫誠一郎
    • Organizer
      第13回分子予防環境医学研究会
    • Place of Presentation
      和歌山県民文化会館
    • Year and Date
      2014-01-31
    • Related Report
      2013 Annual Research Report
  • [Presentation] 環境汚染化学物質の周産期曝露による表現型変化-エピジェネティクスと環境毒性学-2012

    • Author(s)
      大迫誠一郎
    • Organizer
      日本獣医学会
    • Place of Presentation
      大宮ソニックシティ(埼玉県)(招待講演)
    • Year and Date
      2012-03-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胚性幹細胞試験を用いたメチル水銀の神経発生毒性の影響評価2012

    • Author(s)
      大迫誠一郎, 永野麗子, 何小明, 今西哲, 赤沼宏美, 山根順子, 藤渕航, 曽根秀子
    • Organizer
      日本衛生学会
    • Place of Presentation
      京都大学(京都府)
    • Year and Date
      2012-03-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胎生期ダイオキシン曝露による仔のエピゲノム変化の解析2012

    • Author(s)
      青木礼恵, 栗田尚佳, 遠山千春, 大迫誠一郎
    • Organizer
      分子予防環境医学研究
    • Place of Presentation
      倉敷市民会館(岡山県)
    • Year and Date
      2012-01-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトES細胞を用いた神経系誘導培養系におけるAhrアゴニストの影響.2012

    • Author(s)
      大迫誠一郎,山根順子,今西哲,遠山千春.
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Effects of Ahr agonist on neuronal cell differentiation from human ES cells.2012

    • Author(s)
      Seiichiroh Ohsako, Junko Yamane, Satoshi Imanishi, Chiharu Tohyama
    • Organizer
      The 10th Annual Meeting of International Society for Stem Cell Research
    • Place of Presentation
      Yokohama
    • Related Report
      2012 Annual Research Report
  • [Presentation] 環境汚染物質の胎生期曝露による生後の化学発癌感受性亢進とエピゲノム変化2011

    • Author(s)
      大迫誠一郎
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      幕張メッセ(千葉県)(招待講演)
    • Year and Date
      2011-11-10
    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi