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Effect of epigenetic aberrations on germ cells and interchromosomal coordination of gene expression in mouse spermatogenesis

Research Project

Project/Area Number 16K15173
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionNagasaki University

Principal Investigator

KOJI Takehiko  長崎大学, 医歯薬学総合研究科(医学系), 教授 (30170179)

Co-Investigator(Kenkyū-buntansha) 柴田 恭明  長崎大学, 医歯薬学総合研究科(医学系), 講師 (80253673)
遠藤 大輔  長崎大学, 医歯薬学総合研究科(医学系), 助教 (90516288)
末松 貴史  長崎大学, 医歯薬学総合研究科(医学系), 技術職員 (70264249)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsDNAメチル化 / ヒストン修飾 / アポトーシス / PGK1 / PGK2 / in situ PCR / 精子形成過程 / マウス精巣 / DNAのメチル化 / ヒストンH3修飾 / 人為制御 / クロマチン分布
Outline of Final Research Achievements

In the present study, we found a gradual increase of CCGG methylation till step 11-12 spermatids in normal mouse spermatogenesis unlike the case of 5-methylcytosine (5MC). To mimic the level of DNA methylation, we injected 5-azadC into mice and found that hypomethylation leads to induce spermatogonial apoptosis. Since acetylation pattern of histone H3 was known to change depending upon differentiation stage of germ cells, we examined the effect of HDAC inhibitors such as valproic acid and SAHA on spermatogenesis. Unlike Na phenylbutylate, spermatogonial apoptosis was induced, indicating the different mechanisms among drugs. When Dnmt1 was knock-downed by shRNA vector transfection, the expression of 5MC was markedly decreased, accompanying abnormalities in chromosomal distribution in pachytene spermatocytes. However, the analysis of the distance between PGK1 and PGK2 genes by in situ PCR was not successful in tissue sections, indicating a better use of isolated germ cells.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Analysis of H3K27me3 expression and DNA methylation at CCGG sites in smoking and non-smoking patients with non-small cell lung cancer and their clinical significance.2018

    • Author(s)
      Zhu K, Deng Y, Weng G, Hu D, Huang C, Matsumoto K, Nagayasu T, Koji T, Zheng X, Jiang W, Lin G, Cai Y, Weng G, Chen X
    • Journal Title

      Oncol Lett

      Volume: 15 Pages: 6179-6188

    • DOI

      10.3892/ol.2018.8100

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Changes in DNA Methylation of Oocytes and Granulosa Cells Assessed by HELMET during Folliculogenesis in Mouse Ovary2018

    • Author(s)
      Liu J, Zhang W, Wu Z, Dai L, Koji T
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 51 Issue: 2 Pages: 93-100

    • DOI

      10.1267/ahc.17039

    • NAID

      130006727960

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model2017

    • Author(s)
      Sasabe R, Sakamoto J, Goto K, Honda Y, Kataoka H, Nakano J, Origuchi T, Koji T, Okita M
    • Journal Title

      J Orthop Res

      Volume: in press Issue: 9 Pages: 1998-2006

    • DOI

      10.1002/jor.23498

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 5-aza-2'-deoxycytidine impairs mouse spermatogenesis at multiple stages through different usage of DNA methyltransferases.2016

    • Author(s)
      Song N, Endo D, Song B, Shibata Y, Koji T
    • Journal Title

      Toxicology

      Volume: 361-362 Pages: 62-72

    • DOI

      10.1016/j.tox.2016.07.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.2016

    • Author(s)
      Muta K, Obata Y, Oka S, Abe S, Minami K, Kitamura M, Endo D, Koji T, Nishino T
    • Journal Title

      Nephrol Dial Transplant

      Volume: 96 Issue: 10 Pages: 748-753

    • DOI

      10.1093/ndt/gfw036

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chondroitin sulfate prevents peritoneal fibrosis in mice by suppressing NF-κB activation.2016

    • Author(s)
      Abe S, Obata Y, Oka S, Koji T, Nishino T, Izumikawa K
    • Journal Title

      Med Mol Morphol

      Volume: 49 Issue: 3 Pages: 144-153

    • DOI

      10.1007/s00795-016-0133-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model2016

    • Author(s)
      Ahmed GJ, Tatsukawa E, Morishita K, Shibata Y, Suehiro F, Kamitakahara M, Yokoi T, Koji T, Umeda M, Nishimura M, Ikeda T
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 49 Issue: 3 Pages: 97-107

    • DOI

      10.1267/ahc.16007

    • NAID

      130005161006

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 分子局在解析の歴史と展望。2016

    • Author(s)
      小路武彦
    • Journal Title

      Clinical Neuroscience (脳の見える化‐分子・機能局在編)

      Volume: 34 Pages: 620-624

    • Related Report
      2016 Research-status Report
  • [Presentation] Possible involvement of hypoacetylation of histone H3K9 in estrogen-dependent transdifferentiation of LH cells to PRL cells in male mouse pituitary.2018

    • Author(s)
      Nandar Tun, Myat Thu Soe, Endo D, Shibata Y, Koji T
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Possible involvement of hypoacetylation of histone H3K9 in estrogen-dependent transdifferentiation of LH cells to PRL cells in male mouse pituitary.2018

    • Author(s)
      Nandar Tun, Myat Thu Soe, Endo D, Shibata Y, Koji T
    • Organizer
      46th Myanmar Health Research Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Possible involvement of hypoacetylation of histone H3K9 in estrogen-dependent transdifferentiation of LH/FSH cells to PRL cells in male mouse pituitary.2017

    • Author(s)
      Nandar Tun, Myat Thu Soe, Endo D, Shibata Y, Koji T
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎大学坂本キャンパス(長崎県長崎市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Simultaneous detection of multiple mRNAs using FRET based molecular beacon probes by in situ hybridization.2017

    • Author(s)
      Choijookhuu N, Ishizuka T, Xu Y, Koji T, Hishikawa Y
    • Organizer
      日本顕微鏡学会第60回記念シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 分子組織細胞化学の最新の進歩と形態学の未来。2017

    • Author(s)
      小路武彦
    • Organizer
      神奈川歯科大学学会第52回総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 精子形成過程に於けるエピゲノム動態とその意義。2017

    • Author(s)
      小路武彦
    • Organizer
      第58回日本組織細胞化学会総会・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] マウス精子形成細胞核におけるPGK遺伝子座の分布変化とmRNA発現解析 -In situ PCR並びにIn situハイブリダイゼーションを用いて-。2017

    • Author(s)
      柴田恭明、遠藤大輔、小路武彦
    • Organizer
      第58回日本組織細胞化学会総会・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] マウス精母細胞に於けるDnmt1発現抑制が共局在因子の核内発現に及ぼす影響の解析。2017

    • Author(s)
      遠藤大輔、柴田恭明、小路武彦
    • Organizer
      第58回日本組織細胞化学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Differentiation-dependent changes in DNA methylation and histone H3 acetylation: Possible roles of these epigenetic factors in mouse spermatogenesis.2017

    • Author(s)
      Koji T
    • Organizer
      The 12th China-Japan Joint Seminar on Histochemistry and Cytochemistry
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エピジェネティック因子:細胞動態の新たな組織細胞化学的パラメーター。2017

    • Author(s)
      小路武彦
    • Organizer
      第36回分子病理学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] マウス精母細胞に於いて染色体動態を制御するDnmt1と共局在する核内因子の解析。2016

    • Author(s)
      遠藤大輔、柴田恭明、小路武彦
    • Organizer
      第48回日本臨床分子形態学会総会・学術集会
    • Place of Presentation
      くまもと県民交流館パレア(熊本県熊本市)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] A new approach: FRET based molecular beacon fluorescent probe for in situ hybridization.2016

    • Author(s)
      Narantsog C, Ishizuka T, Xu Y, Koji T, Hishikawa, Y
    • Organizer
      第57回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      杏林大学井の頭キャンパス(東京都三鷹市)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Book] ライフサイエンス 顕微鏡学ハンドブック2018

    • Author(s)
      小路武彦
    • Total Pages
      344
    • Publisher
      朝倉書店
    • Related Report
      2017 Annual Research Report
  • [Book] 組織細胞化学20162016

    • Author(s)
      小路武彦
    • Total Pages
      220
    • Publisher
      学際企画株式会社
    • Related Report
      2016 Research-status Report
  • [Remarks] 組織細胞生物学分野ホームページ

    • URL

      http://www.med.nagasaki-u.ac.jp/anatomy3/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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