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Study of DNA methylation and gene expression during development of male reproductive organs. -Global analysis of DNA methylation using Restriction Landmark Genomic Scanning (RLGS) method-

Research Project

Project/Area Number 14370004
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionChiba University

Principal Investigator

MORI Chisato  Chiba university, graduate school of medicine, professor, 大学院・医学研究院, 教授 (90174375)

Co-Investigator(Kenkyū-buntansha) FUKATA Hideki  Chiba university, graduate school of medicine, associate professor, 大学院・医学研究院, 助教授 (00359598)
KOMIYAMA Masatoshi  Chiba university, center for environment, health and field sciences, lecturer, 講師 (70175339)
KODA Masao  Chiba university, graduate school of medicine, assistant professor, 大学院・医学研究院, 助手 (50361449)
TODAKA Emiko  Chiba university, center for environment, health and field sciences, assistant professor, 助手 (30334212)
足達 哲也  千葉大学, 大学院・医学研究院, 助手 (60345014)
櫻井 健一  千葉大学, 大学院・医学研究院, 助教授 (80323434)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsreproductive organ / development / DNA methylation / RLGS method / gene expression / endocrine disruptor / diethylstilbestrol / epigenetics / DNAメチレーション
Research Abstract

Neonatal C57BL/6 mice were exposed to 3 μg/pup/day of synthetic estrogen, diethylstilbestrol(DBS). At day 30, epididymidis (from male mice) and uteri (from female mice) were teken, and their status of DNA methylation were analyzed using restriction landmark genomic scanning method (RLGS). In epididymis and uterus, the methylation of 7 and 11 loci (out of about 1000 loci) were changed, respectively. Then lower dose of DBS (0.3、0.03、0.003 μg/pup/day) were examined, and clear dose dependency of the methylation change was observed.
We analyzed the loci those methylation were changed by DBS. Four loci from epididymis and 3 loci from uterus were cloned, and the characteristics of them such as GC content, chromosomal distribution, neighbor genes were examined. Four loci from epididymis were near from zinc finger protein, RNA helicase, protein kinase associated gene, retinal disease associated gene, respectively. Three loci from uterus were not close to known genes.
The mechanism by which methylation was changed, and the effect of that change on development of male reproductive organs remained to be elucidated.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (63 results)

All 2005 2004 2003 2002 Other

All Journal Article (32 results) Book (3 results) Publications (28 results)

  • [Journal Article] Necessity to measure PCBs and organochlorine pesticide concentrations in human umbilical cords for fetal exposure assessment.2005

    • Author(s)
      Hideki Fukata
    • Journal Title

      Environmental Health Perspectives 113

      Pages: 297-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of the effect of phytoestrogen, daidzein, on a testicular cell line, using mRNA and protein expression profile.2005

    • Author(s)
      Adachi, Tetsuya
    • Journal Title

      Food and Chemical Toxicology 42

      Pages: 445-452

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of sulfasalazine on sperm acrosome reaction and gene expression in the male reproductive organs of rats.2005

    • Author(s)
      Fukushima, Tamio
    • Journal Title

      Toxicological Sciences

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Necessity to measure PCBs and organochlorine pesticide concentrations in human umbilical cords for fetal exposure assessment.2005

    • Author(s)
      Fukata, Hideki
    • Journal Title

      Environmental Health Perspectives 113

      Pages: 297-303

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An experimental trial to establish risk communication as a tool to decrease the risk by exposure to multiple chemicals for the future generations.2005

    • Author(s)
      Todaka, Emiko
    • Journal Title

      Reproductive Medicine and Biology

    • NAID

      10015566619

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fetal exposure to phytoestrogens - the difference of phytoestrogen status in mother and fetus.2005

    • Author(s)
      Todaka, Emiko
    • Journal Title

      Environmental Research

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Epigenetic alteration by the chemical substances, food and environmental factors.2004

    • Author(s)
      Fukata, Hideki
    • Journal Title

      Reproductive Medicine and Biology 3

      Pages: 115-121

    • NAID

      10013503607

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice : toxicogenomic analysis using cDNA microarray.2004

    • Author(s)
      Adachi, Tetsuya
    • Journal Title

      Food and Chemical Toxicology 42

      Pages: 445-452

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Toxicogenomic difference between diethylstilbestrol and 17β-estradiol in mouse testicular gene expression by neonatal exposure.2004

    • Author(s)
      Adachi, Tetsuya
    • Journal Title

      Molecular Reproductive Development 67

      Pages: 19-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression analysis of the rat testis after treatment with di(2-ethlhexyl) phthalate using cDNA microarray and real-time RT-PCR.2004

    • Author(s)
      Kijima, Kazuyasu
    • Journal Title

      Toxicology and Applied Pharmacology 200

      Pages: 103-110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of neonatal exposure to diethylstilbestrol on testicular gene expression in adult mouse : comprehensive analysis with cDNA subt-raction method.2004

    • Author(s)
      Matsuno, Yoshiharu
    • Journal Title

      International Journal of Andrology 27

      Pages: 115-122

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] High-risk group and high-risk life stage : Key issues in adverse effects of environmental agents on human health.2004

    • Author(s)
      Mori, Chisato
    • Journal Title

      Reproductive Medicine and Biology 3

      Pages: 51-58

    • NAID

      10013086238

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Percoll fractionation of adult mouse spermatogonia improves germ cell transplantation.2004

    • Author(s)
      Koh, Kyu-Bom
    • Journal Title

      Asian Journal of Andrology 6

      Pages: 93-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Flutamide induces ultrastructural changes in spermatids and the ectoplasmic specialization between the Sertoli cell and spermatids in mouse testes.2004

    • Author(s)
      Anahara, Reiko
    • Journal Title

      Reproductive Toxicology 18

      Pages: 589-596

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 胎児を基準とした化学物質のリスク評価と対策の開発の試み2004

    • Author(s)
      深田秀樹
    • Journal Title

      ファルマシア 40

      Pages: 328-332

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epigenetic alteration by the chemical substances, food and environ-mental factors.2004

    • Author(s)
      Hideki Fukata
    • Journal Title

      Reproductive Medicine and Biology 3

      Pages: 115-121

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice : toxicogenomic analysis using cDNA microarray.2004

    • Author(s)
      Tetsuya Adachi
    • Journal Title

      Food and Chemical Toxicology 42

      Pages: 445-452

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Toxicogenomic difference between diethylstilbestrol and 17β-estradiol in mouse testicular gene expression by neonatal exposure.2004

    • Author(s)
      Tetsuya Adachi
    • Journal Title

      Molecular Reproductive Development 67

      Pages: 19-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression analysis of the rat testis after treatment with di(2-ethylhexyl) phthalate using cDNA microarray and real-time RT-PCR.2004

    • Author(s)
      Kazuyasu Kijima
    • Journal Title

      Toxicology and Applied Pharmacology 200

      Pages: 103-110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of neonatal exposure to diethylstilbestrol on testicular gene expression in adult mouse : comprehensive analysis with cDNA subt-raction method.2004

    • Author(s)
      Yoshiharu Matsuno
    • Journal Title

      International Journal of Andrology 27

      Pages: 115-122

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] High-risk group and high-risk life stage : Key issues in adverse effects of environmental agents on human health.2004

    • Author(s)
      Chisato Mori
    • Journal Title

      Reproductive Medicine and Biology 3

      Pages: 51-58

    • NAID

      10013086238

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Percoll fractionation of adult mouse spermatogonia improves germ cell transplantation.2004

    • Author(s)
      Kyu-Bom Koh
    • Journal Title

      Asian Journal of Andrology 6

      Pages: 93-98

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Flutamide induces ultrastructural changes in spermatids and the ectoplasmic specialization between the Sertoli cell and spermatids in mouse testes.2004

    • Author(s)
      Reiko Anahara
    • Journal Title

      Reproductive Toxicology 18

      Pages: 589-596

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of neonatal exposure to diethylstilbestrol on testicular gene expression in adult mouse : comprehensive analysis with cDNA subtraction method.2004

    • Author(s)
      Matsuno, Yoshiharu
    • Journal Title

      International Journal of Andrology 27

      Pages: 115-122

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene expression analysis of the rat testis after treatment with di(2-ethylhexyl) phthalate using cDNA microarray and real-time RT-PCR.2004

    • Author(s)
      Kijima, Kazuyasu
    • Journal Title

      Toxicology and Applied Pharmacology 200

      Pages: 103-110

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pilot study to reduce dioxins in the human body.2004

    • Author(s)
      Sakurai, Kenichi
    • Journal Title

      Internal Medicine 43

      Pages: 792-795

    • NAID

      130000085086

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association of testicular undescent induced by prenatal flutamide treatment with thickening of the cremaster muscle in rats.2003

    • Author(s)
      Matsuno, Yoshiharu
    • Journal Title

      Reproductive Medical Biology 2

      Pages: 109-113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection of mitomycin C-induced testicular toxicity by micronucleus assay in mice.2003

    • Author(s)
      Nakagawa, Soichi
    • Journal Title

      Reproductive Medicine and Biology 2

      Pages: 69-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of testicular undescent induced by prenatal flutamide treatment with thickening of the cremaster muscle in rats.2003

    • Author(s)
      Yoshiharu Matsuno
    • Journal Title

      Reproductive Medical Biology 2

      Pages: 109-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection of mitomycin C-induced testicular toxicity by micronucleus assay in mice.2003

    • Author(s)
      Soichi Nakagawa
    • Journal Title

      Reproductive Medicine and Biology 2

      Pages: 69-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Temporal changes in testis-weight during the last 50 years in Japan.2002

    • Author(s)
      Mori, Chisato
    • Journal Title

      Anatomical Science International 77

      Pages: 109-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Temporal changes in testis-weight during the last 50 years in Japan.2002

    • Author(s)
      Chisato Mori
    • Journal Title

      Anatomical Science International 77

      Pages: 109-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 新編精子学2005

    • Author(s)
      森 千里
    • Publisher
      東京大学出版会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 未来世代のために -新米医学部教授の七転八倒-2004

    • Author(s)
      森 千里
    • Total Pages
      215
    • Publisher
      環境新聞社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 未来世代のために-新米医学部教授の七転八倒-2004

    • Author(s)
      森 千里
    • Total Pages
      215
    • Publisher
      環境新聞社
    • Related Report
      2004 Annual Research Report
  • [Publications] Adachi, Tetsuya: "Toxicogenomic difference between diethylstilbestrol and 17beta-estradiol in mouse testicular gene expression by neonatal exposure."Mol.Reprod.Dev.. 67・1. 19-25 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Adachi, Tetsuya: "Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice."Food Chem.Toxicol.. 42・3. 445-452 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakurai, Kenichi: "Bisphenol A affects glucose transport in mouse 3T3-F442A adipocytes."Br.J.Pharmacol.. 141・2. 209-214 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Adachi, Tetsuya: "ADAM7 (a disintegrin and metalloprotease 7) mRNA is suppressed in mouse epididymis by neonatal exposure to diethylstilbestrol."Mol.Reprod.Dev.. 64・4. 414-421 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuno, Yoshiharu: "Association of testicular undescent induced by prenatal flutamide treatment with thickening of the cremaster muscle in rats."Reprod Med Biol. 2・3. 109-113 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori, Chisato: "Application of toxicogenomic analysis to risk assessment of delayed long-term effects of multiple chemicals including endocrine disruptors in human fetuses."Environ.Health Perspect.. 111. 803-809 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagawa, Soichi: "Detection of mitomycin C-induced testicular toxicity by micronucleus assay in mice."Reprod Med Biol. 2・2. 69-72 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakurai Kenichi: "An experimental model using guinea pigs to reduce accumulated dioxins in the body."Congenit.Anom.Kyoto.. 42・4. 323-326 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori, Chisato: "Temporal changes in testis weight during the past 50 years in Japan."Anat.Sci.Int.. 77・2. 109-116 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 森 千里: "胎児の複合汚染状況の情報開示と次世代環境健康学の創成について"産婦人科の実際. 52. 2363-2371 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 森 千里: "ヒト胎児の複合曝露に対する新しい影響評価法の開発-トキシコゲノミクヌを用いて"医学のあゆみ. 204. 954-958 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 森 千里: "化学物質による胎児の複合汚染 ハイリスクグループの存在と「次世代環境健康学」創生の必要性"科学. 74. 38-42 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小宮山 政敏: "環境ホルモンの最新動向と測定・試験・機器開発"シーエムシー出版. 4 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 森 千里: "胎児の複合汚染"中央公論社. 204 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori, Chisato: "Application of toxicogenomic analysis to risk assessment of delayed long-term effects of multiple chemicals including endocrine disruptors in human fetuses"Environ.Health Perspect.Toxicogenomics. 111・1T. 7-13 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uchida, Kaoru: "Bisphenol-A administration during pregnancy results in fetal exposure in mice and monkeys"J.Health Sci.. 48・6. 579-582 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tobe, Toyofusa: "Embryonic myosin heavy chain and troponin T isoforms remain in creamaster muscle of adult cryptorchid rats induced with flutamide"Arch.Histol.Cytol.. 65・3. 279-290 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yang, Ya-Gai: "Immunohistochemical changes of androgen receptor and estrogen receptors alpha and beta in the gubernaculum of cryptorchid rats during testicular descent"Acta histochem.Cytochem.. 35・4. 281-286 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori, Chisato: "Temporal changes in testis-weight during the last 50 years in Japan"Anatomical Science International. 77. 109-116 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Todaka, Emiko: "Necessity to establish new risk assessment and risk communication for human fetal exposure to multiple endocrine disruptors in Japan"Congenital Anomalies. 42. 87-93 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Adachi, Tetsuya: "Toxicogenomic effects of neonatal exposure to diethylstilbestrol on mouse testicular gene expression in the long term : a study using cDNA microarray analysis"Mol.Reprod.Dev.. 63. 17-23 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Adachi, Tetsuya: "ADAM7 (a disintegrin and metalloprotease 7) mRNA is suppressed in mouse epididymis by neonatal exposure to diethylstilbestrol"Mol.Reprod.Dev.. 64・4. 414-421 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura, Noriko: "Sorting specificity of spermatogenic cell specific region of mouse hexokinase-s (mHk1-s)"Mol.Reprod.Dev.. 64. 113-119 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takano, Kaiya: "Alteration of androgen receptor immunoexpression by neonatal DES-treatment in mouse epididymis"Congenital Anomalies. 42. 36-37 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 足達 哲也: "実験講座マイクロアレイの使い方:内分泌撹乱物質による遺伝子発現変化のモニタリング"ゲノム医学. 2. 399-405 (2002)

    • Related Report
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  • [Publications] 小宮山 政敏: "胎児複合曝露の影響評価"医学のあゆみ. 201. 137-142 (2002)

    • Related Report
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  • [Publications] Komiyama, Masatoshi: "Analysis of toxicogenomic response to endocrine disruptors in the mouse testis. In : Toxicogenomics. T.Inoue and W.D.Pennie(eds)"Springer-Verlag Tokyo. 7 (2003)

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  • [Publications] 森 千里: "胎児の複合汚染"中央公論社. 204 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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