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Molecular mechanism of programing of the adaptation to environment: search for the epigenomic modification alteration in the germ line

Research Project

Project/Area Number 23658237
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Basic veterinary science/Basic zootechnical science
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)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsエピジェネティクス / 化学物質 / 後世代影響 / メチル化 / 生殖細胞 / 進化 / 肝臓 / 薬物代謝酵素
Research Abstract

As a preliminary experiment, epigenomes of the male offspring born form the non-exposed females mated to F1 males exposed to dioxin (TCDD) during fetal stage. The methylation frequency of CpG of Cyp1a1 promoter region located on -500 of transcription start site of exposed animals was similar with that of the control in an epididymis sperm, liver, and kidney. Thus, it was suggested that trans-generational effects were not obtained. Next, hypomethylation was examined in the hepatoma Hep1c1c7 cells, but any methylation were not observed in CpGs of Cyp1a1 promoter region. Therefore we decided to focus on the hypomethylation of the liver in the C57BL/6J F1 mice exposed TCDD on E12.5. Hypomethylation of CpG was found to begin to occur from birth day 3 in the liver. Using these neonatal liver samples, ChIP assay with three types of DNA methyl-transferases were carried out. The binding of Dnmt1 and Dnmt3b to Cyp1a1 promoter region was found to significantly decrease by TCDD exposure.

Report

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

    (23 results)

All 2014 2013 2012 2011

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (12 results)

  • [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 Final Research Report
    • Peer Reviewed / Open Access
  • [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 ligands2013

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

      Mol Pharmacol

      Volume: 85, 113(published ahead of print) Issue: 2 Pages: 279-289

    • DOI

      10.1124/mol.113.088856

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inference of Gene Regulatory Networks to Detect Toxicity-Specific Effects in Human Embryonic Stem Cells2013

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

      Intl J Adv Life Sci

      Volume: v5 n 1&2

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [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 diet2013

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

      J Applied Toxicol

      Volume: (in press)

    • Related Report
      2013 Final 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
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status 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
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells.2012

    • Author(s)
      Akanuma H, Qin XY, Nagano R, Win-Shwe TT, Imanishi S, Zaha H, Yoshinaga J, Fukuda T, Ohsako S, and Sone H.
    • Journal Title

      Front Genet

      Volume: 3 Pages: 141-141

    • DOI

      10.3389/fgene.2012.00141

    • Related Report
      2013 Final Research Report 2012 Research-status 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
      2013 Final Research Report 2012 Research-status 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
      2013 Final Research Report 2012 Research-status 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
      2013 Final Research Report 2012 Research-status Report 2011 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Presentation] Prediction of Developmental Neurotoxic Effects using Human Pluripotent Stem Cells2014

    • Author(s)
      Junko Yamane, Sachiyo Aburatani, Satoshi Imanishi, Reiko Nagano, Hideko Sone, Seiichiroh Ohsako, and Wataru Fujibuchi
    • Organizer
      The 7th Takeda Science Foundation Symposium on PharmaSciences iPS Cells in Drug Discovery & Development, International Symposium 2014
    • Place of Presentation
      京都, 京都大学iPS研究所
    • Year and Date
      2014-01-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Generation of the human ES cell line driven by dioxin responsive reporter gene2013

    • Author(s)
      Seiichiroh Ohsako
    • Organizer
      The 11st Annual Meeting of International Society for Stem Cell Research
    • Place of Presentation
      Boston, USA
    • Year and Date
      2013-06-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Effects of 2, 3, 7, 8-tetrachlorodibenzo -p-dioxin in the neuronal differentiation system using human embryonic stem cells2012

    • Author(s)
      Seiichiroh Ohsako, Junko Yamane, Chiharu Tohyama
    • Organizer
      Dioxin2012
    • Place of Presentation
      Carinz, Australia
    • Year and Date
      2012-08-31
    • Related Report
      2013 Final Research Report
  • [Presentation] Effects of Ahr agonist on neuronal cell differentiation from human ES cells2012

    • 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, Japan
    • Year and Date
      2012-06-16
    • Related Report
      2013 Final 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, パシフィコ横浜
    • Year and Date
      2012-06-12
    • Related Report
      2013 Final 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
      さいたま, 大宮ソニックシティ
    • Year and Date
      2012-03-28
    • Related Report
      2013 Final 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 Research-status 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 Research-status 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(招待講演)
    • Place of Presentation
      大宮ソニックシティ(埼玉県)
    • Related Report
      2011 Research-status 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)
    • Related Report
      2011 Research-status 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)
    • Related Report
      2011 Research-status 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(招待講演)
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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