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2013 Fiscal Year Final Research Report

Aberrant DNA methylation of imprinted loci in sperm from infertile men and the causal mechanism

Research Project

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Project/Area Number 23390385
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTohoku University

Principal Investigator

ARIMA Takahiro  東北大学, 医学(系)研究科(研究院), 教授 (80253532)

Co-Investigator(Kenkyū-buntansha) OKAE Hiroaki  東北大学, 大学院・医学系研究科, 助教 (10582695)
HIURA Hitoshi  東北大学, 大学院・医学系研究科, 助教 (70451523)
MIYAUCHI Naoko  東北大学, 大学院・医学系研究科, 技術補佐員 (60596162)
Co-Investigator(Renkei-kenkyūsha) YAEGASHI Nobuo  東北大学, 大学院・医学系研究科, 教授 (00241597)
NAKAI Kunihiko  東北大学, 大学院・医学系研究科, 教授 (00291336)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords生殖医学 / ゲノムインプリンティング
Research Abstract

Recent studies indicate the possibility of excess imprinting disease occurrence in babies by assisted reproductive technologies (ART). Genomic imprinting is regulated with epigenetic DNA methylation and the allele-specific expression of certain genes. In this study, we examined the DNA methylation status of 22 imprinted genes by bisulphite-based methylation analyses in sperm DNA from male ART patients. We found 43 patients (25.4%) whose sperm had abnormal DNA methylation among the sperm samples of men from 197 infertile couples. In addition, we found that abnormal spermatogenesis (leading to low sperm counts) is associated with defective methylation. These results would be of value in determining the safest and most ethical approach to use in ART.

  • Research Products

    (24 results)

All 2013 2012 2011

All Journal Article (13 results) (of which Peer Reviewed: 12 results) Presentation (8 results) (of which Invited: 4 results) Book (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Stability of the abnormal imprinting of human induced pluripotent stem cells2013

    • Author(s)
      Hiura H, Toyoda M, Okae H, Sakurai M, Miyauchi N, Sato A, Kiyokawa N, Okita H, Miyagawa Y, Akutsu H, Nishino K, Umezawa A, Arima T
    • Journal Title

      BMC Genetics

      Volume: 14 Pages: 32

    • DOI

      10.1186/1471-2156-14-32

    • Peer Reviewed
  • [Journal Article] ヒト生殖補助医療(ART) とエピジェネティクスの異常2013

    • Author(s)
      千葉初音, 岡江寛明, 有馬隆博
    • Journal Title

      遺伝子医学

      Volume: MOOK25号 Pages: 178-183

    • URL

      http://www.bioweb.ne.jp/content/idensi/idensi_mook0025.html

    • Peer Reviewed
  • [Journal Article] 生殖細胞と酸化ストレス2013

    • Author(s)
      井原基公, 有馬隆博
    • Journal Title

      医学のあゆみ

      Volume: 247(9) Pages: 851-855

    • URL

      http://www.ishiyaku.co.jp/magazines/ayumi/AyumiArticleDetail.aspx?BC=286400&AC=13310

    • Peer Reviewed
  • [Journal Article] Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproductive technologies2012

    • Author(s)
      Hiura H, Okae H, Miyauchi N, Sato F, Sato A, Van De PetteM, John R M, KagamiM, Nakai K, Soejima H, Ogata T, Arima T
    • Journal Title

      Human Reproduction

      Volume: 27 (8) Pages: 2541-2548

    • DOI

      10.1093/humrep/des197

    • Peer Reviewed
  • [Journal Article] High-throughput detection of aberrant imprint methylation in the ovarian cancer by the bisulphite PCR-Luminex method2012

    • Author(s)
      Hiura H, Okae H, KobayashiH, Miyauchi N, Sato F, Sato A, Suzuki F, Nagase S, Sugawara J, Nakai K, Yaegashi N, Arima T
    • Journal Title

      BMC Medical Genomics

      Volume: 5 Pages: 8-17

    • DOI

      10.1186/1755-8794-5-8

    • Peer Reviewed
  • [Journal Article] Distribution and Y397 phosphorylation of focal adhesion kinase on follicular development in the mouse ovary2012

    • Author(s)
      Sakurai M, Ohtake J, Ishikawa T, Tanemura K, Hoshino Y, Arima T, Sato E
    • Journal Title

      Cell and Tissue

      Volume: 347 Pages: 457-465

    • DOI

      10.1007/s00441-011-1307-2

    • Peer Reviewed
  • [Journal Article] Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression2012

    • Author(s)
      Okae H, Hiura H, Nishida Y, Funayama R, Tanaka S, Chiba H, Yaegashi N, Nakayama K, Sasaki H, Arima T
    • Journal Title

      Hum Mol Genet

      Volume: 10 (3) Pages: 548-558

    • DOI

      10.1093/hmg/ddr488

    • Peer Reviewed
  • [Journal Article] The physical ability of elderly female Japanese patients with cerebrovascular disease correlates with the telomere length in their peripheral blood leukocytes2011

    • Author(s)
      Maeda T, Oyama J, Sasaki M, Nishiyama Y, Kudo Y, Yamori T, Nakazono T, Arima T, Makino N
    • Journal Title

      Aging Clinical and Experimental Research

      Volume: 57 Pages: 137-143

    • DOI

      10.1159/000314633

    • Peer Reviewed
  • [Journal Article] The correlation between the clinical laboratory data and the telomere length in peripheral blood leukocytes of Japanese female patients with hypertension2011

    • Author(s)
      Maeda T, Oyama J, Sasaki M, Arima T, Makino N
    • Journal Title

      The Journal of Nutrition, Health and Aging (JNHA)

      Volume: 15 Pages: 240-244

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21369674

    • Peer Reviewed
  • [Journal Article] The physical ability of Japanese female elderly with cerebrovascular disease correlates to the telomere length and subtelomeric methylation status in their peripheral blood leukocytes2011

    • Author(s)
      Maeda T, Oyama J, Higuchi Y, Nishiyama Y, Kudo Y, Yamori Y, Nakazono T, Arima T, Mimori K, Makino N
    • Journal Title

      Gerontology

      Volume: 57 Pages: 137-143

    • DOI

      10.1159/000314633

    • Peer Reviewed
  • [Journal Article] Assessing loss of imprint methylation in sperm from subfertile men using novel methylation polymerase chain reaction Luminex analysis2011

    • Author(s)
      Sato A, Hiura H, Okae H, Miyauchi N, Abe Y, Utsunomiya T, Yaegashi N, Arima T
    • Journal Title

      Fertil and Steril

      Volume: 95 Pages: 129-134

    • DOI

      10.1016/j.fertnstert.2010.06.076

    • Peer Reviewed
  • [Journal Article] Role for piRNAs and non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus2011

    • Author(s)
      Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy P.J, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway P.D. & Sasaki H
    • Journal Title

      Science

      Volume: 332 Pages: 848-852

    • DOI

      10.1126/science.1203919

    • Peer Reviewed
  • [Journal Article] ART におけるエピジェティクス異常産婦人科の実際2011

    • Author(s)
      有馬隆博, 樋浦仁, 岡江寛明, 佐藤晶子, 宮内尚子, 阿部千鶴, 林千賀
    • Journal Title

      金原出版株式会社

      Pages: 741-750

    • URL

      http://search.jamas.or.jp/link/ui/2011191627

  • [Presentation] ART と先天異常2013

    • Author(s)
      有馬隆博
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      江陽グランドホテル, 仙台
    • Year and Date
      2013-11-22
    • Invited
  • [Presentation] ART とゲノムインプリンティング2013

    • Author(s)
      有馬隆博
    • Organizer
      第58回日本生殖医学会学術講演会・総会
    • Place of Presentation
      神戸ポートピアホテル, 神戸
    • Year and Date
      2013-11-16
  • [Presentation] 基礎から臨床へ, ART とエピゲノム2013

    • Author(s)
      有馬隆博
    • Organizer
      第31回日本受精着床学会総会・学術講演会
    • Place of Presentation
      別府 シンポジウム
    • Year and Date
      2013-08-09
  • [Presentation] 生殖領域におけるエピジェネティクス研究の最前線2013

    • Author(s)
      有馬隆博
    • Organizer
      第54回日本卵子学会
    • Place of Presentation
      学術総合センター2 階一橋記念講堂, 東京
    • Year and Date
      2013-05-25
    • Invited
  • [Presentation] 生殖補助医療と小児科医療の接点2013

    • Author(s)
      有馬隆博
    • Organizer
      第116回日本小児科学会学術集会
    • Place of Presentation
      広島市文化交流会館, 広島
    • Year and Date
      2013-04-20
    • Invited
  • [Presentation] 乏精子症とゲノムインプリンティング2013

    • Author(s)
      千葉初音, 有馬隆博
    • Organizer
      日本生殖再生医学会・第8回学術集会
    • Place of Presentation
      シェーンバッハ・サボー, 東京
    • Year and Date
      2013-03-10
  • [Presentation] 生殖医療とエピジェネティクス2012

    • Author(s)
      有馬隆博
    • Organizer
      第11回学術集会日本不妊カウンセリング学会
    • Place of Presentation
      東京
    • Year and Date
      2012-06-08
    • Invited
  • [Presentation] ART におけるエピジェネティク機構2012

    • Author(s)
      有馬隆博
    • Organizer
      日本生殖再生医学会・第7回学術集会
    • Place of Presentation
      東京
    • Year and Date
      2012-03-25
  • [Book] DNA METHYLATION, Aberrant DNA methylation of imprinted loci in male and female germ cells of infertile couples2012

    • Author(s)
      Arima T, Okae H, Hiura H, Miyauchi N, Sato F, Sato A, Hayashi C
    • Total Pages
      29:183-192
    • Publisher
      INTECH
  • [Book] 卵子学2011

    • Author(s)
      有馬隆博, 樋浦仁, 岡江寛明, 佐藤晶子, 宮内尚子
    • Total Pages
      122-131
    • Publisher
      京都大学学術出版会
  • [Patent(Industrial Property Rights)] ヒト精子の質的機能評価システムに応用するDNA メチル化解析システムの開発2012

    • Inventor(s)
      有馬 隆博
    • Industrial Property Rights Holder
      東北大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      P20110420 PCT 出願
    • Filing Date
      2012-05-16
    • Overseas

URL: 

Published: 2015-06-25  

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