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Epigenetic mechanisms of valproate-induced polycystic ovary syndrome in epilepsy patients

Research Project

Project/Area Number 25462568
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSapporo Medical University

Principal Investigator

Endo Toshiaki  札幌医科大学, 医学部, 研究員 (90213595)

Co-Investigator(Kenkyū-buntansha) 鈴木 拓  札幌医科大学, 医学部, 教授 (20381254)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords多嚢胞性卵巣症候群 / PCOS / androgen / insulin resistance / epigenetics / valproic acid / HDAC inhibitor / アンドロゲン / バルプロ酸 / エピジェネティクス / 多嚢胞卵巣 / インスリン抵抗性 / epilepsy
Outline of Final Research Achievements

Valproic acid(VPA) is well known to be a HDAC inhibitor. When women have taken VPA for epilepsy from their childhood, their ovarian morphology revealed to be polycystic ovary. When VPA was given for pregnant rats, their daughters' ovary revealed to be PCO. Hypermethylation of DNA of the daughter's rats is reported when androgen is given them during pregnancy. In this study, the daughter's ovary revealed to be polycystic ovary. Zucker fa/fa rats with insulin resistance is reported to have hypermethylation of DNA and have polycystic ovary. When we gave pioglitazone(a PPARγactivator) for Zucker fa/fa rats , we succeeded in reduction of small follicles in their ovary. In these results, we realized the existence of very curious relationship between PCOS and epigenome.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2016 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Failure of GnRH agonist-triggered oocyte maturation: its cause and management2013

    • Author(s)
      Asada Y, Ito F, Honnma H, Takiguchi S, Fukunaga N, Hashiba Y, Baba T, Endo T.
    • Journal Title

      J Assist Reprod Genet

      Volume: 30 Issue: 4 Pages: 581-585

    • DOI

      10.1007/s10815-013-9966-4

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Assisted reproductive technique increases the risk of placental polyp.2013

    • Author(s)
      Baba T, Endo T, Ikeda K, Shimizu A, Morishita M, Kuno Y, Honnma H, Kiya T, Ishioka S, Saito T.
    • Journal Title

      Gynecol Endocrinol

      Volume: 29 Issue: 6 Pages: 611-614

    • DOI

      10.3109/09513590.2013.788636

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Pioglitazone is effective for multiple phenotypes of the Zucker fa/fa rats used as a model of polycystic ovary syndrome with insulin resistance2016

    • Author(s)
      T.Endo,Morishita M, Kuno Y, Honnma H, Baba T, Kiya T, Saito T.
    • Organizer
      ESHRE annual meeting 2016
    • Place of Presentation
      Helsinki, Finland
    • Year and Date
      2016-07-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラットPCOモデルを用いた妊娠時の高アンドロゲンとインスリン抵抗性の雌仔への生 後影響について2016

    • Author(s)
      森下美幸
    • Organizer
      第68回日本産科婦人科学会総会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Year and Date
      2016-04-22
    • Related Report
      2015 Research-status Report
  • [Presentation] バルプロン酸投与てんかん症例に発症した2次性多嚢胞性卵巣症候群の特徴について2013

    • Author(s)
      久野芳佳、遠藤俊明、清水亜由美、森下美幸、池田桂子、馬場剛、斎藤豪
    • Organizer
      日本産科婦人科学会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Book] PCOSの診断、図説よくわかる臨床不妊症学 一般不妊症編2016

    • Author(s)
      遠藤俊明
    • Publisher
      中外医学社
    • Related Report
      2016 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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