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Mechanistic Elucidation of Embryo Implantation and Development of Novel Biomarkers for Endometrial Receptivity

Research Project

Project/Area Number 23K15827
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Matsuo Mitsunori  東京大学, 医学部附属病院, 助教 (00823618)

Project Period (FY) 2023-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsimplantation failure / Embryo Implantation / Lif / Stat3 / LIF / 着床 / 着床不全 / 子宮内膜 / 子宮頸部 / 生殖補助医療 / 着床障害 / 着床能
Outline of Research at the Start

体外受精胚移植において、着床障害は診断・治療法が未だ確立していない難治性疾患である。本研究は子宮頸部上皮に発現する遺伝子解析による子宮の着床能の新規診断法の開発を目的とする。
野生型/着床障害マウスモデルの着床期子宮を用いて、着床の成否依存的に変化する子宮頸部細胞のマーカー遺伝子を選出する。さらにヒト着床期の子宮頸部細胞を用いて、着床期ヒト子宮頸部細胞に発現する着床の成否依存的に変化する遺伝子を選出する。
本研究によって、基礎医学の側面では子宮頸部と子宮体部(内膜)の遺伝子発現の同期性を明らかにでき、臨床医学の側面では胚移植施行を妨げない非侵襲的な着床能の新規診断法の開発に繋がる。

Outline of Final Research Achievements

Recurrent implantation failure is a major challenge in assisted reproductive medicine. In this study, we focused on the synchrony of gene expression between the cervix and endometrium to develop a non-invasive method for evaluating implantation potential. Analysis of the implantation period in mice and humans revealed that LIF (leukemia inhibitory factor) is highly expressed in cervical epithelium during the implantation period, similar to the endometrium. Furthermore, LIF was found to be expressed in the epithelium prior to embryo attachment and in the stroma after attachment, contributing to embryo attachment and embryo development, respectively. These results indicate that LIF is an essential factor for successful implantation and suggest the potential for non-invasively evaluating endometrial receptivity by measuring LIF expression in cervical epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

本研究により、反復着床不全における子宮内膜の分子異常、特にLIF-STAT3経路の胚着床における機能が関与することが明らかとなった。これらの因子は反復着床障害の治療において、新たなバイオマーカーや治療標的となる可能性がある。さらに、ヒト子宮内膜試料でも同様の傾向が確認され、臨床応用の可能性が示唆された。本成果をもとにRIF患者の病態分類が進めば、より精密な診断と個別化医療の実現が可能となり、難治性不妊の克服に向けた重要な一歩となる。学術的にも子宮内膜機能の理解に新たな視点を与える成果である。

Report

(3 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • Research Products

    (10 results)

All 2025 2024 2023

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (3 results)

  • [Journal Article] Comparison of diagnostic tests for chronic endometritis and endometrial dysbiosis in recurrent implantation failure: Impact on pregnancy outcomes2025

    • Author(s)
      Hiratsuka Daiki、Matsuo Mitsunori、Kashiwabara Kosuke、Inoue Mariko、Ishizawa Chihiro、Iida Rei、Fukui Yamato、Aikawa Shizu、Hiraoka Takehiro、Harada Miyuki、Wada-Hiraike Osamu、Osuga Yutaka、Hirota Yasushi
    • Journal Title

      Scientific Reports

      Volume: 15 Issue: 1 Pages: 8272-8272

    • DOI

      10.1038/s41598-025-92906-9

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hysteroscopic Endometrial Defect Following Adenomyomectomy and Incidence of Placenta Accreta Spectrum and Uterine Rupture Complications for Subsequent Pregnancy2025

    • Author(s)
      Ichinose Mari、Iriyama Takayuki、Hiraike Osamu、Sayama Seisuke、Hashimoto Ayako、Suzuki Kensuke、Matsuo Mitsunori、Toshimitsu Masatake、Seyama Takahiro、Sone Kenbun、Kumasawa Keiichi、Hirota Yasushi、Osuga Yutaka
    • Journal Title

      Reproductive Sciences

      Volume: 32 Issue: 2 Pages: 467-473

    • DOI

      10.1007/s43032-024-01758-7

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Foxa2-dependent uterine glandular cell differentiation is essential for successful implantation2025

    • Author(s)
      Jia Zhaoyu、Li Bo、Matsuo Mitsunori、Dewar Amanda、Mustafaraj Anxhela、Dey Sudhansu K.、Yuan Jia、Sun Xiaofei
    • Journal Title

      Nature Communications

      Volume: 16 Issue: 1

    • DOI

      10.1038/s41467-025-57848-w

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatiotemporally distinct roles of cyclooxygenase-1 and cyclooxygenase-2 at fetomaternal interface in mice2024

    • Author(s)
      Aikawa Shizu、Matsuo Mitsunori、Akaeda Shun、Sugimoto Yukihiko、Arita Makoto、Isobe Yosuke、Sugiura Yuki、Taira Shu、Maeda Rae、Shimizu-Hirota Ryoko、Takeda Norihiko、Hiratsuka Daiki、He Xueting、Ishizawa Chihiro、Iida Rei、Fukui Yamato、Hiraoka Takehiro、Harada Miyuki、Wada-Hiraike Osamu、Osuga Yutaka、Hirota Yasushi
    • Journal Title

      JCI Insight

      Volume: 9 Issue: 19

    • DOI

      10.1172/jci.insight.181865

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatiotemporal functions of leukemia inhibitory factor in embryo attachment and implantation chamber formation2024

    • Author(s)
      Aikawa Shizu、Hiraoka Takehiro、Matsuo Mitsunori、Fukui Yamato、Fujita Hidetoshi、Saito-Fujita Tomoko、Shimizu-Hirota Ryoko、Takeda Norihiko、Hiratsuka Daiki、He Xueting、Ishizawa Chihiro、Iida Rei、Akaeda Shun、Harada Miyuki、Wada-Hiraike Osamu、Ikawa Masahito、Osuga Yutaka、Hirota Yasushi
    • Journal Title

      Cell Death Discovery

      Volume: 10 Issue: 1 Pages: 481-481

    • DOI

      10.1038/s41420-024-02228-4

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenomyosis with uterine abscess formation treated by adenomyomectomy: A report of two cases2024

    • Author(s)
      Hiratsuka Daiki、Ishizawa Chihiro、Iida Rei、Fukui Yamato、Matsuo Mitsunori、Nishida Masato、Ikemura Masako、Harada Miyuki、Wada‐Hiraike Osamu、Osuga Yutaka、Hirota Yasushi
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 51 Issue: 1

    • DOI

      10.1111/jog.16185

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The EZH2?PRC2?H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion2023

    • Author(s)
      Fukui Yamato、Hirota Yasushi、Aikawa Shizu、Sakashita Akihiko、Shimizu-Hirota Ryoko、Takeda Norihiko、Ishizawa Chihiro、Iida Rei、Kaku Tetsuaki、Hirata Tomoyuki、Hiraoka Takehiro、Akaeda Shun、Matsuo Mitsunori、Osuga Yutaka
    • Journal Title

      Cell Death & Disease

      Volume: 14 Issue: 5 Pages: 320-320

    • DOI

      10.1038/s41419-023-05832-x

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 遺伝子改変マウスモデルを駆使した子宮内膜機能解析に基づく反復着床不全の予測法の確立2024

    • Author(s)
      松尾 光徳
    • Organizer
      2024年 第76回日本産科婦人科学会 学術講演会シンポジウム 「難治性不妊症の新規診断・治療法の開発に向けた病態解明」
    • Related Report
      2024 Annual Research Report
  • [Presentation] Foxa2 deletion in mouse uterine glands causes embryonic diapause2023

    • Author(s)
      Mitsunori Matsuo, Jia Yuan, Amanda Bartos, Yasushi Hirota, Yutaka Osuga, Sudhansu K Dey, Xiaofei Sun
    • Organizer
      IFFS 2023 World Congress
    • Related Report
      2023 Research-status Report
  • [Presentation] 子宮におけるEZH2-PRC2-H3K27me3経路が胚浸潤において果たす役割2023

    • Author(s)
      福井 大和, 廣田 泰, 藍川 志津, 石沢 千尋, He Xueting, 飯田 麗, 赤枝 俊, 平岡 毅大, 松尾 光徳, 大須賀 穣
    • Organizer
      第41回日本受精着床学会
    • Related Report
      2023 Research-status Report

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Published: 2023-04-13   Modified: 2026-01-16  

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