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2018 Fiscal Year Annual Research Report

Uterine hypoxia inducible factor regulates embryo implantation

Research Project

Project/Area Number 16H04679
Research InstitutionThe University of Tokyo

Principal Investigator

廣田 泰  東京大学, 医学部附属病院, 講師 (40598653)

Co-Investigator(Kenkyū-buntansha) 藤田 知子  東京大学, 医学部附属病院, 特任研究員 (60375441)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords着床 / 子宮内膜 / 間質 / 管腔上皮 / トロホブラスト / 低酸素誘導因子 / マウスモデル
Outline of Annual Research Achievements

正常な着床過程では、子宮内膜管腔上皮と間質との間の基底膜に間隙が生まれその間隙にトロホブラストが浸潤することを示した。子宮全体のHIF2α欠損マウスでは着床部位の子宮内膜上皮と間質とを境界する基底膜に間隙が生じずトロホブラスト浸潤が起きず着床障害をきたした。間質からの子宮内膜管腔上皮の剥離と胚浸潤は、子宮内膜間質のHIF2α欠損マウスでも同様に認められなかったが、子宮内膜上皮のHIF2α欠損マウスは正常の胚浸潤と着床を示した。このことから、子宮内膜間質細胞のHIF2αが管腔上皮剥離と胚浸潤を調節していることが示された。子宮内膜間質のHIF2αが調節している分子として、LOX、MT2-MMP、VEGF、ADMが同定され、胚着床を制御する低酸素関連因子が示された。子宮のHIF2αが管腔上皮の剥離と胚浸潤をコントロールする必須因子であることが解明された。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

  • Research Products

    (25 results)

All 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (22 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 22 results,  Open Access: 12 results) Remarks (2 results)

  • [Int'l Joint Research] シンシナティ小児病院(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      シンシナティ小児病院
  • [Journal Article] Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations2019

    • Author(s)
      Inoue S, Hirota Y, Ueno T, Fukui Y, Yoshida E, Hayashi T, Kojima S, Takeyama R, Hashimoto T, Kiyono T, Ikemura M, Taguchi A, Tanaka T, Tanaka Y, Sakata S, Takeuchi K, Muraoka A, Osuka S, Saito T, Oda K, Osuga Y, Terao Y, Kawazu M, Mano H.
    • Journal Title

      Nature Communications

      Volume: 10 Pages: 5785

    • DOI

      10.1038/s41467-019-13708-y

    • Peer Reviewed / Open Access
  • [Journal Article] Accumulation of advanced glycation end products in follicles is associated with poor oocyte developmental competence2019

    • Author(s)
      Takahashi Nozomi、Harada Miyuki、Azhary Jerilee M K、Kunitomi Chisato、Nose Emi、Terao Hiromi、Koike Hiroshi、Wada-Hiraike Osamu、Hirata Tetsuya、Hirota Yasushi、Koga Kaori、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Molecular Human Reproduction

      Volume: 25 Pages: 684~694

    • DOI

      10.1093/molehr/gaz050

    • Peer Reviewed / Open Access
  • [Journal Article] Endometriosis Triggers Excessive Activation of Primordial Follicles via PI3K-PTEN-Akt-Foxo3 Pathway2019

    • Author(s)
      Takeuchi Arisa、Koga Kaori、Satake Erina、Makabe Tomoko、Taguchi Ayumi、Miyashita Mariko、Takamura Masashi、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Yoshino Osamu、Wada-Hiraike Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 104 Pages: 5547~5554

    • DOI

      10.1210/jc.2019-00281

    • Peer Reviewed / Open Access
  • [Journal Article] A survey of public attitudes toward uterus transplantation, surrogacy, and adoption in Japan2019

    • Author(s)
      Nakazawa Akari、Hirata Tetsuya、Arakawa Tomoko、Nagashima Natsuki、Fukuda Shinya、Neriishi Kazuaki、Harada Miyuki、Hirota Yasushi、Koga Kaori、Wada-Hiraike Osamu、Koizumi Yoshio、Fujii Tomoyuki、Irahara Minoru、Osuga Yutaka
    • Journal Title

      PLOS ONE

      Volume: 14 Pages: e0223571

    • DOI

      10.1371/journal.pone.0223571

    • Peer Reviewed / Open Access
  • [Journal Article] Placental expression of lysophosphatidic acid receptors in normal pregnancy and preeclampsia2019

    • Author(s)
      Fujii Tatsuya、Nagamatsu Takeshi、Schust Danny J.、Ichikawa Mayuko、Kumasawa Keiichi、Yabe Shinichiro、Iriyama Takayuki、Hirota Yasushi、Osuga Yutaka、Aoki Junken、Yatomi Yutaka、Fujii Tomoyuki
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 82 Pages: e13176

    • DOI

      10.1111/aji.13176

    • Peer Reviewed
  • [Journal Article] Clinical aspects and management of inguinal endometriosis: A case series of 20 patients2019

    • Author(s)
      Arakawa Tomoko、Hirata Tetsuya、Koga Kaori、Neriishi Kazuaki、Fukuda Shinya、Ma Suke、Sun Hui、Nagashima Natsuki、Harada Miyuki、Hirota Yasushi、Wada‐Hiraike Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 45 Pages: 2029~2036

    • DOI

      10.1111/jog.14059

    • Peer Reviewed
  • [Journal Article] Cell Cycle Perturbation Induces Collagen Production in Fibroblasts2019

    • Author(s)
      Wake Masaki、Takeda Norihiko、Isagawa Takayuki、Sato Tatsuyuki、Nakagama Yu、Morioka Masaki Suimye、Hirota Yasushi、Asagiri Masataka、Maemura Koji、Manabe Ichiro、Tanabe Kazuaki、Komuro Issei
    • Journal Title

      International Heart Journal

      Volume: 60 Pages: 958~963

    • DOI

      10.1536/ihj.18-710

    • Peer Reviewed
  • [Journal Article] Role of oxidative stress in follicular fluid on embryos of patients undergoing assisted reproductive technology treatment2019

    • Author(s)
      Terao Hiromi、Wada‐Hiraike Osamu、Nagumo Aiko、Kunitomi Chisato、Azhary Jerilee M. K.、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Koga Kaori、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 45 Pages: 1884~1891

    • DOI

      10.1111/jog.14040

    • Peer Reviewed
  • [Journal Article] Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M2019

    • Author(s)
      Abe H, Takeda N, Isagawa T, Semba H, Nishimura S, Morioka MS, Nakagama Y, Sato T, Soma K, Koyama K, Wake M, Katoh M, Asagiri M, Neugent ML, Kim JW, Stockmann C, Yonezawa T, Inuzuka R, Hirota Y, Maemura K, Yamashita T, Otsu K, Manabe I, Nagai R, Komuro I.
    • Journal Title

      Nature Communications

      Volume: 10 Pages: 2824

    • DOI

      10.1038/s41467-019-10859-w

    • Peer Reviewed / Open Access
  • [Journal Article] Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation2019

    • Author(s)
      Fukui Yamato、Hirota Yasushi、Matsuo Mitsunori、Gebril Mona、Akaeda Shun、Hiraoka Takehiro、Osuga Yutaka
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 18 Pages: 234~240

    • DOI

      10.1002/rmb2.12280

    • Peer Reviewed
  • [Journal Article] Endothelial Cells in the Decidual Bed Are Potential Therapeutic Targets for Preterm Birth Prevention2019

    • Author(s)
      Deng Wenbo、Yuan Jia、Cha Jeeyeon、Sun Xiaofei、Bartos Amanda、Yagita Hideo、Hirota Yasushi、Dey Sudhansu K.
    • Journal Title

      Cell Reports

      Volume: 27 Pages: 1755~1768.e4

    • DOI

      10.1016/j.celrep.2019.04.049

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Contralateral ovarian endometrioma recurrence after unilateral salpingo-oophorectomy2019

    • Author(s)
      Hidari Tokie、Hirata Tetsuya、Arakawa Tomoko、Koga Kaori、Neriishi Kazuaki、Fukuda Shinya、Nakazawa Akari、Nagashima Natsuki、Ma Suke、Sun Hui、Takamura Masashi、Harada Miyuki、Hirota Yasushi、Wada-Hiraike Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      BMC Women's Health

      Volume: 19 Pages: 59

    • DOI

      10.1186/s12905-019-0760-z

    • Peer Reviewed
  • [Journal Article] Activation of Nrf2/Keap1 pathway by oral Dimethylfumarate administration alleviates oxidative stress and age-associated infertility might be delayed in the mouse ovary2019

    • Author(s)
      Akino Nana、Wada-Hiraike Osamu、Isono Wataru、Terao Hiromi、Honjo Harunori、Miyamoto Yuichiro、Tanikawa Michihiro、Sone Kenbun、Hirano Mana、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Koga Kaori、Oda Katsutoshi、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Reproductive Biology and Endocrinology

      Volume: 17 Pages: 23

    • DOI

      10.1186/s12958-019-0466-y

    • Peer Reviewed / Open Access
  • [Journal Article] Progesterone governs endometrial proliferation-differentiation switching and blastocyst implantation2019

    • Author(s)
      Hirota Yasushi
    • Journal Title

      Endocrine Journal

      Volume: 66 Pages: 199~206

    • DOI

      10.1507/endocrj.EJ18-0431

    • Peer Reviewed / Open Access
  • [Journal Article] Endoplasmic Reticulum Stress Activated by Androgen Enhances Apoptosis of Granulosa Cells via Induction of Death Receptor 5 in PCOS2018

    • Author(s)
      Azhary Jerilee M K、Harada Miyuki、Takahashi Nozomi、Nose Emi、Kunitomi Chisato、Koike Hiroshi、Hirata Tetsuya、Hirota Yasushi、Koga Kaori、Wada-Hiraike Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Endocrinology

      Volume: 160 Pages: 119~132

    • DOI

      10.1210/en.2018-00675

    • Peer Reviewed / Open Access
  • [Journal Article] A survey of public attitudes towards third-party reproduction in Japan in 20142018

    • Author(s)
      Yamamoto Naoko、Hirata Tetsuya、Izumi Gentaro、Nakazawa Akari、Fukuda Shinya、Neriishi Kazuaki、Arakawa Tomoko、Takamura Masashi、Harada Miyuki、Hirota Yasushi、Koga Kaori、Wada-Hiraike Osamu、Fujii Tomoyuki、Irahara Minoru、Osuga Yutaka
    • Journal Title

      PLOS ONE

      Volume: 13 Pages: e0198499

    • DOI

      10.1371/journal.pone.0198499

    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Nerve Injury-Induced Protein1 (Ninj1) in Endometriosis2018

    • Author(s)
      Miyashita Mariko、Koga Kaori、Takeuchi Arisa、Makabe Tomoko、Taguchi Ayumi、Urata Yoko、Izumi Gentaro、Takamura Masashi、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Wada-Hiraike Osamu、Yoshino Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Reproductive Sciences

      Volume: 26 Pages: 1105~1110

    • DOI

      10.1177/1933719118806395

    • Peer Reviewed
  • [Journal Article] The efficacy of non-assisted reproductive technology treatment might be limited in infertile patients with advanced endometriosis in their 30s2018

    • Author(s)
      Isono Wataru、Wada-Hiraike Osamu、Akino Nana、Terao Hiromi、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Koga Kaori、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 45 Pages: 368~375

    • DOI

      10.1111/jog.13826

    • Peer Reviewed
  • [Journal Article] Mdm2‐p53‐SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality2018

    • Author(s)
      Haraguchi Hirofumi、Hirota Yasushi、Saito-Fujita Tomoko、Tanaka Tomoki、Shimizu-Hirota Ryoko、Harada Miyuki、Akaeda Shun、Hiraoka Takehiro、Matsuo Mitsunori、Matsumoto Leona、Hirata Tetsuya、Koga Kaori、Wada-Hiraike Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      The FASEB Journal

      Volume: 33 Pages: 2610~2620

    • DOI

      10.1096/fj.201801401R

    • Peer Reviewed
  • [Journal Article] HIF2α in the uterine stroma permits embryo invasion and luminal epithelium detachment2018

    • Author(s)
      Matsumoto Leona、Hirota Yasushi、Saito-Fujita Tomoko、Takeda Norihiko、Tanaka Tomoki、Hiraoka Takehiro、Akaeda Shun、Fujita Hidetoshi、Shimizu-Hirota Ryoko、Igaue Shota、Matsuo Mitsunori、Haraguchi Hirofumi、Saito-Kanatani Mayuko、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Journal of Clinical Investigation

      Volume: 128 Pages: 3186~3197

    • DOI

      10.1172/JCI98931

    • Peer Reviewed / Open Access
  • [Journal Article] Thoracic endometriosis syndrome: Comparison between catamenial pneumothorax or endometriosis-related pneumothorax and catamenial hemoptysis2018

    • Author(s)
      Fukuda Shinya、Hirata Tetsuya、Neriishi Kazuaki、Nakazawa Akari、Takamura Masashi、Izumi Gentaro、Harada Miyuki、Hirota Yasushi、Koga Kaori、Wada-Hiraike Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      European Journal of Obstetrics & Gynecology and Reproductive Biology

      Volume: 225 Pages: 118~123

    • DOI

      10.1016/j.ejogrb.2018.04.021

    • Peer Reviewed
  • [Journal Article] Activation of Nrf2 might reduce oxidative stress in human granulosa cells2018

    • Author(s)
      Akino Nana、Wada-Hiraike Osamu、Terao Hiromi、Honjoh Harunori、Isono Wataru、Fu Houju、Hirano Mana、Miyamoto Yuichiro、Tanikawa Michihiro、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Koga Kaori、Oda Katsutoshi、Kawana Kei、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 470 Pages: 96~104

    • DOI

      10.1016/j.mce.2017.10.002

    • Peer Reviewed / Open Access
  • [Remarks] 胚が子宮内膜に浸潤する着床のメカニズムを解明

    • URL

      http://www.h.u-tokyo.ac.jp/vcms_lf/release_20180619.pdf

  • [Remarks] 子宮腺筋症と子宮内膜症併発に関連する遺伝子変異を発見―発症機構の解明に期待―

    • URL

      https://www.ncc.go.jp/jp/information/pr_release/2019/1219/20191219.pdf

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Published: 2021-01-27  

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