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Analysis of human endometrial cell apoptosis in interface of implantation

Research Project

Project/Area Number 16K11110
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 Sayaka  慶應義塾大学, 医学部(信濃町), 助教 (60445236)

Co-Investigator(Kenkyū-buntansha) 丸山 哲夫  慶應義塾大学, 医学部(信濃町), 准教授 (10209702)
内田 浩  慶應義塾大学, 医学部(信濃町), 講師 (90286534)
升田 博隆  慶應義塾大学, 医学部(信濃町), 講師 (80317198)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords着床 / 細胞死 / 子宮内膜上皮細胞 / 細胞運動 / 生殖医学
Outline of Final Research Achievements

It is well known that human endometrial epithelial cells (EECs) fall into apoptosis in interface between embryo and EECs.
To unveil effective role of EEC apoptosis, we tested the ability of cell adhesion, cell proliferation, and cell motility in EECs stimulated by EEC contents derived from Fas Ab-induced apoptosis and mechanical breaking. Apoptotic EEC contents showed no regulation of EEC proliferation, small up-regulation of cell adhesion against embryo, and acceleration of cell motility. Stimulation by EEC contents obtained from mechanical crushing induced significant acceleration of EEC motility, but not EEC proliferation and adhesion ability.
These results indicate that apoptotic EEC nearby implantation point probably assist successful implantation through up-regulation of EEC motion.

Academic Significance and Societal Importance of the Research Achievements

これまで着床局面における子宮内膜上皮細胞の細胞死はあくまでも胚の陥入ルート形成のためと解釈されてきたが、細胞死によって着床局所に漏出する子宮内膜上皮細胞の内容が周囲に影響を及ぼす可能性がある。検討の結果、子宮内膜上皮細胞の増殖には影響を及ぼさないものの細胞運動には加速方向に影響しうることが判明した。また胚との接着能がやや上昇する結果が得られた。
これらの結果は、胚接着後に細胞死に陥った子宮内膜上皮細胞の細胞内容は周囲にパラクライン様式で影響し、着床局面の子宮内膜上細胞の運動を促進し、胚の陥入ルート形成を加速させ、胚との接着能を高めることでより安定した着床成立に寄与している可能性が考えられた。

Report

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

    (19 results)

All 2019 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (10 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] Impact of borderline-subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss.2017

    • 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: -

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Debris makes “MR DC” hustle on endometriosis.2017

    • Author(s)
      Maruyama T
    • Journal Title

      Fertil Steril.

      Volume: 107 Issue: 1 Pages: 68-68

    • DOI

      10.1016/j.fertnstert.2016.10.014

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytogenetic analysis of spontaneously discharged products of conception by array-based comparative genomic hybridization.2016

    • Author(s)
      Ozawa N, Sago H, Matsuoka K, Maruyama T, Migita O, Aizu Y, Inazawa J
    • Journal Title

      SpringerPlus.

      Volume: 5 Issue: 1 Pages: 874-874

    • DOI

      10.1186/s40064-016-2594-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [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 (SRI2019)
    • 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
    • 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] 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
  • [Presentation] Impact of subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss2017

    • Author(s)
      Sayaka Uchida, Tetsuo Maruyama, Maki Kagami, Fumie Miki, Hanako Hihara, Shoko Tomisato, Satomi Katakura, Yushi Yoshimasa, Hirotaka Masuda, Hiroshi Uchida, Mamoru Tanaka, Daisuke Aoki
    • Organizer
      第69回日本産科婦人科学会
    • 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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