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Analysis of uterine natural killer cells and retinoid metabolism pathway during decidualization of human endometrial stromal cells

Research Project

Project/Area Number 25861508
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionJuntendo University

Principal Investigator

Kuroda Keiji  順天堂大学, 医学部, 准教授 (60459162)

Research Collaborator OZAKI Rie  順天堂大学, 医学部, 大学院生
OCHIAI Asako  順天堂大学, 医学部, 大学院生
IKEMOTO Yuko  順天堂大学, 医学部, 大学院生
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords子宮内膜 / 脱落膜化 / 妊娠 / 習慣流産 / レチノイド / 子宮NK細胞 / レスベラトロール / サーチュイン / 子宮内膜間質細胞 / 子宮内膜脱落膜化 / 細胞分化 / レチノイン酸 / グルココルチコイド
Outline of Final Research Achievements

In pregnancy, decidual transformation of human endometrial stromal cells (HESCs) is essential for embryo implantation. Uterine natural killer (uNK) cells in HESCs induce angiogenesis at implantation, but aberrant elevated uNK cell levels are associated with reproductive failure including recurrent pregnancy loss. We identified that 11βHSD1/GR/MR signaling pathway regulated uNK cells and MR-dependent retinoid (vitamin A) metabolism pathway in primary HESC cultures decidualized in vitro. The wholesale reprogramming of the retinoid signaling, transport, and metabolism pathways in decidualizing HESCs may be critical in limiting exposure of the implanting conceptus in early pregnancy. Furthermore, optimal decidual transformation of primary cultures may involve not only cell differentiation also apoptosis or senescence of specific subpopulations.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results)

  • [Int'l Joint Research] University of Warwick(英国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Elevated Periimplantation Uterine Natural Killer Cell Density in Human Endometrium Is Associated With Impaired Corticosteroid Signaling in Decidualizing Stromal Cells.2013

    • Author(s)
      Kuroda K, Venkatakrishnan R, James S, Sucurovic S, Mulac-Jericevic B, Lucas ES, Takeda S, Shmygol A, Brosens JJ, Quenby S.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 98 Issue: 11 Pages: 4429-37

    • DOI

      10.1210/jc.2013-1977

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 生殖医療における天然型プロゲステロン製剤の新たな可能性ー子宮内膜の研究データを基にー2015

    • Author(s)
      黒田恵司
    • Organizer
      第33回日本受精着床学会総会・学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Abstract title: Decidualization of human endometrial stromal cells regulates cellular and extracellular retinoic acid levels at implantation2015

    • Author(s)
      Rie Ozaki, Keiji Kuroda, Tsutomu Fujimura, Akemi Matsumoto, Atsuo Itakura, Jan J Brosens, Satoru Takeda
    • Organizer
      ESHRE annual meeting 2015
    • Place of Presentation
      ポルトガル リスボン
    • Year and Date
      2015-06-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 天然型プロゲステロン製剤に期待する着床や流産への効果2015

    • Author(s)
      黒田恵司
    • Organizer
      最適な不妊治療カンファレンス
    • Place of Presentation
      東京
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Decrease in intracellular retinoic acid regulates decidual transformation of human endometrial stromal cells2015

    • Author(s)
      Rie Ozaki, Keiji Kuroda, Mari Kitade, Jun Kumakiri, Makoto Jinushi, Azusa Shinjo, Noriko Kato, Yuko Ikemoto, Satoru Takeda
    • Organizer
      IFFS/JSRM international meeting
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト子宮内膜間質細胞内レチノイン酸、レチナール濃度の減少が脱落膜化過程を制御する2015

    • Author(s)
      黒田恵司、尾﨑理恵、北出真理、熊切順、板倉敦夫、竹田省
    • Organizer
      第88回日本内分泌学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト子宮内膜間質細胞における細胞内レチノイン酸濃度の低下が脱落膜化過程を制御する2015

    • Author(s)
      尾﨑理恵、黒田恵司、北出真理、熊切順、地主誠、新城梓、加藤紀子、竹田省
    • Organizer
      第67回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 着床や流産と関与する子宮内膜脱落膜化過程におけるコルチコステロイド・レチノイドシグナル経路2014

    • Author(s)
      黒田恵司
    • Organizer
      第59回日本生殖医学会学術講演会・総会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒト子宮内膜間質細胞脱落膜化に影響を及ぼすレチノイドの代謝経路とその役割の解析2014

    • Author(s)
      尾﨑理恵、黒田恵司、北出真理、熊切順、地主誠、竹田省
    • Organizer
      第59回日本生殖医学会学術講演会・総会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Elevated uterine natural killer cell density in the peri-implantation endometrium is associated with impaired decidualization and insufficient local cortisol biosynthesis2014

    • Author(s)
      Keiji Kuroda, Satoru Takeda, Jan J Brosens
    • Organizer
      46th International Congresson Pathophysiology of Pregnancy
    • Place of Presentation
      東京
    • Year and Date
      2014-09-18 – 2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] A hypothesis of natural embryo selection for implantation and early pregnancy loss2014

    • Author(s)
      Keiji Kuroda
    • Organizer
      The 6th Japan-Korea ART Conference
    • Place of Presentation
      福岡
    • Year and Date
      2014-08-09
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 着床と初期流産におけるNatural embryo selection仮説2014

    • Author(s)
      黒田恵司
    • Organizer
      第32回日本受精着床学会総会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-31 – 2014-08-01
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Aberrant high uterine natural killer cell density in human endometrium is associated with disordered corticosteroid signalling in decidualizing stromal cells2014

    • Author(s)
      Keiji Kuroda, Rie Ozaki, Satoru Takeda
    • Organizer
      第66回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-18 – 2014-04-20
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis of Intracellular Retinoid Storage Pathway Responsible for Recurrent Pregnancy Loss via Mineralocorticoid Receptor in Decidualizing Human Endometrial Stromal Cells.2013

    • Author(s)
      Keiji Kuroda, Satoru Takeda
    • Organizer
      第65回日本産科婦人科学会学術講演会
    • Place of Presentation
      北海道札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] European Society of Human Reproduction and Embryology Annual meeting, Increased density of uterine natural killer cells in the peri-implantation endometrium is associated with inadequate decidualization, local cortisol deficiency, and impaired induction of metabolic enzymes.2013

    • Author(s)
      Radha Venkatakrishnan, Sandra Šućurović, Jan J. Brosens, Siobhan Quenby, Keiji Kuroda
    • Organizer
      European Society of Human Reproduction and Embryology Annual meeting
    • Place of Presentation
      イギリス、ロンドン
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト子宮内膜細胞の子宮NK細胞増加は、子宮内膜脱落膜化異常と局所コルチゾールの生合成やレチノイド代謝酵素の発現の低下と関与する2013

    • Author(s)
      黒田恵司, Quenby Siobhan, 竹田省, Brosens J Jan.
    • Organizer
      第31回日本受精着床学会総会・学術講演会
    • Place of Presentation
      大分県別府
    • Related Report
      2013 Research-status Report
  • [Presentation] 習慣流産と関与する、ヒト子宮内膜細胞の子宮NK細胞の異常増加は、膜脱落膜化マーカーやレチノイド代謝酵素の発現の低下と関与する2013

    • Author(s)
      黒田恵司, Quenby Siobhan, 竹田省, Brosens J Jan.
    • Organizer
      日本生殖医学会・学術講演会・総会
    • Place of Presentation
      兵庫県神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] Corticosteroid Signaling Related to Idiopathic Recurrent Pregnancy Loss in Decidualizing Human Endometrial Stromal Cells

    • Author(s)
      Keiji Kuroda
    • Organizer
      The 5th Korea-Japan ART conference in conjunction with the 22nd Scientific Meeting of the Korean Society for Assisted Reproduction.
    • Place of Presentation
      韓国 釜山
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 子宮内膜の研究から見た着床と流産の新しいメカニズム

    • Author(s)
      黒田恵司
    • Organizer
      第23回平成不妊研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2022-01-31  

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