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Analysis of human endometrial cell dynamics during human implantation

Research Project

Project/Area Number 16K11109
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

UCHIDA Hiroshi  慶應義塾大学, 医学部(信濃町), 講師 (90286534)

Co-Investigator(Kenkyū-buntansha) 丸山 哲夫  慶應義塾大学, 医学部(信濃町), 准教授 (10209702)
升田 博隆  慶應義塾大学, 医学部(信濃町), 講師 (80317198)
内田 明花  慶應義塾大学, 医学部(信濃町), 助教 (60445236)
日原 華子  慶應義塾大学, 医学部(信濃町), 助教 (80626458)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords着床 / 上皮間充織転換 / EMT / 子宮内膜上皮細胞 / 子宮内膜間質細胞 / 生殖医学
Outline of Final Research Achievements

To improve the ratio of successful implantation in in vitro fertilization and embryo transfer, we investigated whether the orchestrated coordination between endometrial epithelial and stromal cells functions in human implantation, controlling epithelio-mesenchymal transition.
We have reported that one of histone deacetylase inhibitors (SAHA) can induce the morphological change and up-regulation of differentiation marker proteins in human endometrial epithelial cells (EECs), as ovarian steroid hormones can do. In this study, we found that tumor growth factor beta and a kind of interleukins also could induce the morphological change and differentiation in EECs. Furthermore, the stimulants can also up-regulate the cell motility and the adhesion ability to embryo model of EECs. The effect which can assist successful implantation is independent on the regulation by ovarian steroid hormones and histone deacetylase inhibitor.

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、卵巣ステロイドホルモンやヒストン脱アセチル化阻害剤の他にも、ヒト着床における子宮内膜上皮細胞と胚とのインタラクション(着床の初期段階)において、その進行をアシストしうる液性薬剤としてTGFβやある種のインターロイキンが候補になりえることがわかってきた。また、その効果が卵巣ステロイドホルモンによる効果とは別の経路を使っている可能性が示唆された。
当初の目標としていた子宮内膜間質細胞も含めたインタラクションの解明や、EMTを引き起こすトリガー因子の解明にまでは至らなかったため、今後も継続研究を要するが、着床支援治療としてホルモン剤以外の選択肢を増やす可能性を示した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells: Role of the WNT/CTNNB1 Pathway2018

    • Author(s)
      Miyazaki Kaoru、Dyson Matthew T.、Coon V John S.、Furukawa Yuichi、Yilmaz Bahar D.、Maruyama Tetsuo、Bulun Serdar E.
    • Journal Title

      Stem Cell Reports

      Volume: 11 Issue: 5 Pages: 1136-1155

    • DOI

      10.1016/j.stemcr.2018.10.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ZEB1 expression is a potential indicator of invasive endometriosis2017

    • Author(s)
      Furuya M, Masuda H, Hara K, Uchida H, Sato K, Sato S, Asada H, Maruyama T, Yoshimura Y, Katabuchi H, Tanaka M, Saya H
    • Journal Title

      Acta Obstet Gynecol Scand

      Volume: 96 Issue: 9 Pages: 1128-1135

    • DOI

      10.1111/aogs.13179

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of borderline-subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss2017

    • Author(s)
      Uchida S, Maruyama T, Kagami M, Miki F, Hihara H, Katakura S, Yoshimasa Y, Masuda H, Uchida H, Tanaka M
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 43 Issue: 6 Pages: 1014-1020

    • DOI

      10.1111/jog.13319

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Contributions of system A subtypes to α-methylaminoisobutyric acid uptake by placental microvillous membranes of human and rat.2017

    • Author(s)
      Takahashi Y, Nishimura T, Maruyama T, Tomi M, Nakashima E
    • Journal Title

      Amino Acids.

      Volume: 49 Issue: 4 Pages: 795-803

    • DOI

      10.1007/s00726-017-2384-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A case of hysteroscopic resection of cervical pregnancy after successful treatment with systematic methotrexate. J Obstet Gynaecol.2016

    • Author(s)
      Masuda H, Endo T, Yoshimasa Y, Uchida H, Nakabayashi A, Maruyama T, Tanaka M
    • Journal Title

      J Obstet Gynaecol.

      Volume: 36 Issue: 7 Pages: 865-866

    • DOI

      10.1080/01443615.2016.1174837

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] How to create an embryo penetration route.2016

    • Author(s)
      Uchida H, Maruyama T, Masuda H, Uchida S, Miki F, Hihara H, Katakura S, Yoshimasa Y, Tanaka M
    • Journal Title

      Am J Reprod Immunol.

      Volume: 75 Issue: 3 Pages: 326-332

    • DOI

      10.1111/aji.12476

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] P2RY is involved in the migration and invasion of human extravillous trophoblast2019

    • Author(s)
      Tetsuo Maruyama, Satomi Katakura, Tomoka Takao, Toru Arase, Yushi Yoshimasa, Shoko Tomisato, Sayaka Uchida, Hirotaka Masuda, Hiroshi Uchida, Mamoru Tanaka
    • Organizer
      Society for Reproductive Investigation 66th Annual Scientific Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Attempts to establish screening system for identification of drugs targeting human uterine endometrial cancer stem-like cells2018

    • Author(s)
      Tetsuo Maruyama, Tomoka Takao, Hirotaka Masuda, Fumie Miki, Sayaka Uchida, Hiroshi Uchida, Mamoru Tanaka: Attempts to establish screening system for identification of drugs targeting human uterine endometrial cancer stem-like cells
    • Organizer
      International Society for Stem Cell Research 2018 annual meeting (ISSCR2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stem cells solve the enigma of endometriosis?2018

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      4th Congress of the Society of Endometriosis and Uterine Disorders (SEUD2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 子宮内膜幹細胞と上皮間葉転換をターゲットとした非内分泌的な子宮内膜症の新規治療2018

    • Author(s)
      升田博隆,古谷正敬,丸山哲夫,高尾知佳,内田 浩,内田明花,吉政佑之,片倉慧美,吉村泰典,片渕秀隆,田中 守
    • Organizer
      第23回日本生殖内分泌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト正常子宮平滑筋細胞に対する子宮筋腫関連遺伝子MED12の変異導入による機能的病因解析2018

    • Author(s)
      高尾知佳,丸山哲夫,内田 浩,内田明花,三木史恵,片倉慧美,吉政佑之,富里祥子,升田博隆,田中 守
    • Organizer
      第23回日本生殖内分泌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 子宮体癌細胞の幹様細胞とそれを治療標的とする既存薬の探索2018

    • Author(s)
      高尾知佳,升田博隆,三木史恵,片倉慧美,吉政佑之,富里祥子,内田明花,内田 浩,田中 守,丸山哲夫
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト絨毛におけるUDPグルコース膜受容体P2RY14の発現と機能解析2018

    • Author(s)
      片倉慧美,丸山哲夫,瀬田康弘,吉政佑之,富里祥子,日原華子,三木史恵,水口雄貴,内田明花,各務真紀,荒瀬 透,升田博隆,内田 浩,田中 守
    • Organizer
      第63回日本生殖医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 子宮内膜症と上皮間葉転換の関連の解明および上皮間葉転換阻害剤薬のもつ新規子宮内膜症治療薬としての可能性の検討2018

    • Author(s)
      升田博隆,古谷正敬,丸山哲夫,内田 浩,内田明花,吉村泰典,佐谷秀行,片淵秀隆,田中 守
    • Organizer
      第36回日本受精着床学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Anovel approach to treat emdometriosis via targeting epithelial-mesenchymal transition2018

    • Author(s)
      Hirotaka Masuda, Masataka Furuya, Tetsuo Maruyama, Fumie Miki, Satomi Katakura, Yushi Yoshimasa, Sayaka Uchida, Hiroshi Uchida, Tomoka Takao, Hidetaka Katabuchi, Mamoru Tanaka, Daisuke Aoki
    • Organizer
      第70回日本産科婦人科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Differential epithelial-mesenchymal transition status between types of endometriosis and adenomyosis2017

    • Author(s)
      Hirotaka Masuda, Masataka Furuya, Tetsuo Maruyama, Hironori Asada, Hidetaka Katabuchi, Hideyuki Saya, Mamoru Tanaka
    • Organizer
      33rd Annual Meeting of European Society of Human Reproduction and Embryology (ESHRE2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Differential status of epithelial-mesenchymal transition in each endometriotic lesion: ZEB1 as a potential indicator of endometriotic invasiveness2017

    • Author(s)
      Hirotaka Masuda, Masataka Fuyuya, Tetsuo Maruyama, Hironori Asada, Hideyuki Saya, Mamoru Tanaka
    • Organizer
      13th World Congress on Endometriosis (WCE2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 子宮内膜症の各病態における上皮間葉転換状態の解析と子宮内膜症におけるZEB1の浸潤性マーカーとしての可能性2017

    • Author(s)
      升田博隆,古谷正敬,丸山哲夫,内田 浩,内田明花,吉村泰典,佐谷秀行,片渕秀隆,田中 守
    • Organizer
      第35回日本受精着床学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Differential status of epithelial-mesenchymal transition in endometriosis and adenomyosis: ZEBI as a potential indicator of endometriotic invasiveness2017

    • Author(s)
      Hirotaka Masuda, Masataka Furuya, Hironori Asada, Tetsuo Maruyama, Hiroshi Uchida, Sayaka Uchida, Yasunori Yoshimura, Hidetaka Katabuchi, Hideyuki Saya, Mamoru Tanaka, Daisuke Aoki
    • Organizer
      第69回日本産科婦人科学会International Session
    • Related Report
      2017 Research-status Report
  • [Remarks] 慶應義塾大学医学部産婦人科学教室ホームページ

    • URL

      http://www.obgy.med.keio.ac.jp/research/03rep-endo.php

    • Related Report
      2017 Research-status Report
  • [Remarks] 慶應義塾大学医学部産婦人科学教室・生殖内分泌研究室

    • URL

      http://www.obgy.med.keio.ac.jp/research/03rep-endo.php

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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