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Uterine hypoxia inducible factor regulates embryo implantation

Research Project

Project/Area Number 16H04679
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionThe University of Tokyo

Principal Investigator

HIROTA YASUSHI  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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords着床 / 低酸素誘導因子 / 子宮内膜 / 胚 / 間質 / 管腔上皮 / 着床障害 / マウスモデル / トロホブラスト / 低酸素 / HIF / 胎盤 / 子宮 / 胚浸潤 / 増殖因子 / AKT / 胚接着
Outline of Final Research Achievements

This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2α in the whole uterus (Hif2α-uKO mice) showed infertility due to implantation failure. Histological analyses in Hif2α-uKO mice revealed persistence of the intact luminal epithelium, which blocked direct contact between stroma and embryo, inactivation of PI3K-AKT pathway, and failed embryo invasion. Mice with stromal deletion of Hif2α showed infertility with impaired embryo invasion and those with epithelial deletion of Hif2α showed normal fertility, suggesting the importance of stromal HIF2α in embryo invasion. These findings provide new insight that stromal HIF2α allows trophoblast invasion through detachment of the luminal epithelium and activation of an embryonic survival signal.

Academic Significance and Societal Importance of the Research Achievements

着床は胚が子宮内膜に入り込む過程(胚浸潤)を経て成立するが、その仕組みは不明であった。本研究で低酸素誘導因子HIF2aが子宮内膜で作用して胚浸潤を調節していること、子宮内膜間質のHIF2aが子宮内膜管腔上皮を剥離し間質を露出させ胚が子宮内に入り込むのを可能にし、間質が胚とじかに接することによって胚の生存シグナルが活性化すること、が明らかになった(J Clin Invest 2018)。これらの研究成果として胚浸潤の仕組みと胚浸潤の異常による着床障害の機序が世界で初めて解明された。低酸素誘導因子およびその下流因子をターゲットとした着床障害の診断・治療法の開発が期待される。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (61 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (39 results) (of which Int'l Joint Research: 20 results,  Peer Reviewed: 39 results,  Open Access: 33 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results) Book (1 results) Remarks (4 results)

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

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Wayne State University/Cincinnati Children's Hospital/Augusta University(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Cell Cycle Perturbation Induces Collagen Production in Fibroblasts2019

    • Author(s)
      Wake M, Takeda N, Isagawa T, Sato T, Nakagama Y, Morioka MS, Hirota Y, Asagiri M, Maemura K, Manabe I, Tanabe K, Komuro I.
    • Journal Title

      International Heart Journal

      Volume: 60 Issue: 4 Pages: 958-963

    • DOI

      10.1536/ihj.18-710

    • NAID

      130007684138

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2019-07-30
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations2019

    • Author(s)
      Inoue Satoshi、Hirota Yasushi、Ueno Toshihide、十人省略、Tanaka Yosuke、Sakata Seiji、Takeuchi Kengo、Muraoka Ayako、Osuka Satoko、Saito Tsuyoshi、Oda Katsutoshi、Osuga Yutaka、Terao Yasuhisa、Kawazu Masahito、Mano Hiroyuki
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41467-019-13708-y

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 11 Pages: 684-694

    • DOI

      10.1093/molehr/gaz050

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 11 Pages: 5547-5554

    • DOI

      10.1210/jc.2019-00281

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Issue: 10 Pages: 0223571-0223571

    • DOI

      10.1371/journal.pone.0223571

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Issue: 5

    • DOI

      10.1111/aji.13176

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Issue: 10 Pages: 2029-2036

    • DOI

      10.1111/jog.14059

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 9 Pages: 1884-1891

    • DOI

      10.1111/jog.14040

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M.2019

    • 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 Issue: 1 Pages: 2824-2833

    • DOI

      10.1038/s41467-019-10859-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Issue: 3 Pages: 234-240

    • DOI

      10.1002/rmb2.12280

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Rep

      Volume: 27 Issue: 6 Pages: 1755-1768.e4

    • DOI

      10.1016/j.celrep.2019.04.049

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 1 Pages: 59-59

    • DOI

      10.1186/s12905-019-0760-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Issue: 1 Pages: 2323-2323

    • DOI

      10.1186/s12958-019-0466-y

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 3 Pages: 199-206

    • DOI

      10.1507/endocrj.EJ18-0431

    • NAID

      130007626244

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mdm2-p53-SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality2019

    • 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 Issue: 2 Pages: 2610-2620

    • DOI

      10.1096/fj.201801401r

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 1 Pages: 119-132

    • DOI

      10.1210/en.2018-00675

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 10 Pages: 198499-198499

    • DOI

      10.1371/journal.pone.0198499

    • Related Report
      2018 Annual Research Report
    • 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: in press Issue: 8 Pages: 368-375

    • DOI

      10.1177/1933719118806395

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Issue: 2 Pages: 368-375

    • DOI

      10.1111/jog.13826

    • Related Report
      2018 Annual Research Report
    • 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 Issue: 7 Pages: 3186-3197

    • DOI

      10.1172/jci98931

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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

    • Related Report
      2018 Annual Research Report
    • 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

      Mol Cell Endocrinol

      Volume: 470 Pages: 96

    • DOI

      10.1016/j.mce.2017.10.002

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oil-Soluble Contrast Medium (OSCM) for Hysterosalpingography Modulates Dendritic Cell and Regulatory T Cell Profiles in the Peritoneal Cavity: A Possible Mechanism by Which OSCM Enhances Fertility2017

    • Author(s)
      Izumi Gentaro、Koga Kaori、Takamura Masashi、Bo Wang、Nagai Miwako、Miyashita Mariko、Harada Miyuki、Hirata Tetsuya、Hirota Yasushi、Yoshino Osamu、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      J Immunol

      Volume: 198 Issue: 11 Pages: 4277-4284

    • DOI

      10.4049/jimmunol.1600498

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus.2017

    • Author(s)
      Egashira M, Hirota Y, Shimizu-Hirota R, Saito-Fujita T, Haraguchi H, Matsumoto L, Matsuo M, Hiraoka T, Tanaka T, Akaeda S, Takehisa C, Saito-Kanatani M, Maeda K, Fujii T, Osuga Y.
    • Journal Title

      Endocrinology

      Volume: 印刷中 Issue: 7 Pages: 2344-2353

    • DOI

      10.1210/en.2016-1886

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Autotaxin–lysophosphatidic acid–LPA<sub>3</sub> signaling at the embryo-epithelial boundary controls decidualization pathways2017

    • Author(s)
      Aikawa Shizu、Kano Kuniyuki、Inoue Asuka、Wang Jiao、Saigusa Daisuke、Nagamatsu Takeshi、Hirota Yasushi、Fujii Tomoyuki、Tsuchiya Soken、Taketomi Yoshitaka、Sugimoto Yukihiko、Murakami Makoto、Arita Makoto、Kurano Makoto、Ikeda Hitoshi、Yatomi Yutaka、Chun Jerold、Aoki Junken
    • Journal Title

      EMBO J

      Volume: 36 Issue: 14 Pages: 2146

    • DOI

      10.15252/embj.201696290

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nomenclature of primary amenorrhea: A proposal document of the Japan Society of Obstetrics and Gynecology committee for the redefinition of primary amenorrhea2017

    • Author(s)
      Shozu Makio、Ishikawa Hiroshi、Horikawa Reiko、Sakakibara Hideya、Izumi Shun-ichiro、Ohba Takashi、Hirota Yasushi、Ogata Tsutomu、Osuga Yutaka、Kugu Koji
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 43 Issue: 11 Pages: 1738-1742

    • DOI

      10.1111/jog.13442

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis2017

    • Author(s)
      Takahashi Nozomi、Harada Miyuki、Hirota Yasushi、Nose Emi、Azhary Jerilee MK、Koike Hiroshi、Kunitomi Chisato、Yoshino Osamu、Izumi Gentaro、Hirata Tetsuya、Koga Kaori、Wada-Hiraike Osamu、Chang R. Jeffrey、Shimasaki Shunichi、Fujii Tomoyuki、Osuga Yutaka
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 10824-10824

    • DOI

      10.1038/s41598-017-11252-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women.2017

    • Author(s)
      Takahashi N, Harada M, Hirota Y, Zhao L, Azhary JM, Yoshino O, Izumi G, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
    • Journal Title

      Endocrinology

      Volume: 158 Pages: 84-97

    • DOI

      10.1210/en.2016-1511

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Drospirenone reduces inflammatory cytokines, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) expression in human endometriotic stromal cells.2017

    • Author(s)
      Makabe T, Koga K, Miyashita M, Takeuchi A, Sue F, Taguchi A, Urata Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
    • Journal Title

      J Reprod Immunol

      Volume: 119 Pages: 44-48

    • DOI

      10.1016/j.jri.2016.12.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation.2016

    • Author(s)
      Hiraoka T, Hirota Y, Saito-Fujita T, Matsuo M, Egashira M, Matsumoto L, Haraguchi H, Dey SK, Furukawa KS, Fujii T, Osuga Y.
    • Journal Title

      JCI Insight

      Volume: 1 Issue: 8

    • DOI

      10.1172/jci.insight.87591

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing.2016

    • Author(s)
      Deng W, Cha J, Yuan J, Haraguchi H, Bartos A, Leishman E, Viollet B, Bradshaw HB, Hirota Y, Dey SK.
    • Journal Title

      J Clin Invest

      Volume: 126 Issue: 8 Pages: 2941-2954

    • DOI

      10.1172/jci87715

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis.2016

    • Author(s)
      Takeuchi A, Koga K, Miyashita M, Makabe T, Sue F, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
    • Journal Title

      Eur J Obstet Gynecol Reprod Biol

      Volume: 207 Pages: 157-161

    • DOI

      10.1016/j.ejogrb.2016.10.053

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis.2016

    • Author(s)
      Izumi G, Koga K, Takamura M, Makabe T, Nagai M, Urata Y, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
    • Journal Title

      Fertil Steril

      Volume: 107 Issue: 1 Pages: 167-173

    • DOI

      10.1016/j.fertnstert.2016.09.036

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of ovarian cancer after excision of endometrioma.2016

    • Author(s)
      Haraguchi H, Koga K, Takamura M, Makabe T, Sue F, Miyashita M, Urata Y, Izumi G, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Oda K, Kawana K, Fujii T, Osuga Y.
    • Journal Title

      Fertil Steril

      Volume: 106 Issue: 6 Pages: 1432-1437

    • DOI

      10.1016/j.fertnstert.2016.07.1077

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil depletion reduces endometriotic lesion formation in mice.2016

    • Author(s)
      Takamura M, Koga K, Izumi G, Urata Y, Nagai M, Hasegawa A, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
    • Journal Title

      Am J Reprod Immunol

      Volume: 76 Issue: 3 Pages: 193-198

    • DOI

      10.1111/aji.12540

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.2016

    • Author(s)
      Bolnick AD, Bolnick JM, Kilburn BA, Stewart T, Oakes J, Rodriguez-Kovacs J, Kohan-Ghadr HR, Dai J, Diamond MP, Hirota Y, Drewlo S, Dey SK, Armant DR; NICHD National Cooperative Reproductive Medicine Network.
    • Journal Title

      Hum Reprod

      Volume: 31 Issue: 9 Pages: 2042-50

    • DOI

      10.1093/humrep/dew143

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of 1,25-dihydroxy vitamin D3 on endometriosis.2016

    • Author(s)
      Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, Nagai M, Urata Y, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 101 Issue: 6 Pages: 2371-2379

    • DOI

      10.1210/jc.2016-1515

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome.2016

    • Author(s)
      Takahashi N, Harada M, Hirota Y, Zhao L, Yoshino O, Urata Y, Izumi G, Takamura M, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
    • Journal Title

      Mol Cell Endocrinol

      Volume: 428 Pages: 161-169

    • DOI

      10.1016/j.mce.2016.03.032

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells.2016

    • Author(s)
      Taguchi, A., Koga, K., Kawana, K., Makabe, T., Sue, F., Miyashita, M., Yoshida, M., Urata, Y., Izumi, G., Takamura, M., Harada, M., Hirata, T., Hirota, Y., Wada-Hiraike, O., Fujii, T., Osuga, Y
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 75 Issue: 4 Pages: 486-492

    • DOI

      10.1111/aji.12489

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] STAT3: A Key Transcriptional Factor Not Only in Embryo Implantation but also in Endometrial Regeneration2018

    • Author(s)
      Yasushi Hirota
    • Organizer
      Society for Reproductive Investigation, 65th Annual Scientific Meeting, Endometrium Satellite Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Levonorgestrel Inhibits Embryo Implantation by Downregulation of Uterine LIF Expression2018

    • Author(s)
      Mitsunori Matsuo, Yasushi Hirota, Tomoko Saito-Fujita, Hirofumi Haraguchi, Shota Igaue, Leona Matsumoto, Takehiro Hiraoka, Shun Akaeda, Tomoki Tanaka, Tomoyuki Fujii, Yutaka Osuga
    • Organizer
      Society for Reproductive Investigation, 65th Annual Scientific Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activated IL6-STAT3 pathway in adenomyosis2017

    • Author(s)
      Hirota Y, Hiraoka T, Saito-Fujita T, Harada M, Fujii T, Osuga Y.
    • Organizer
      World Conference of Endometriosis 2017
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2017-05-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IL6-STAT3経路の活性化が子宮腺筋症の進展に寄与する2017

    • Author(s)
      廣田泰、平岡毅大、大須賀穣
    • Organizer
      第90回日本内分泌学会学術総会 シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2017-04-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 着床障害の分子機構の解明に基づく着床能の診断法と革新的治療技術の開発2017

    • Author(s)
      廣田泰
    • Organizer
      第69回日本産科婦人科学会学術講演会 シンポジウム
    • Place of Presentation
      広島
    • Year and Date
      2017-04-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 子宮の線維化:子宮腺筋症~IL6/STAT3経路の関与~2017

    • Author(s)
      廣田泰
    • Organizer
      第1回Frontier in basic and clinical research of fibrosis
    • Place of Presentation
      名古屋
    • Year and Date
      2017-03-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Activated IL6-STAT3 pathway in adenomyosis2017

    • Author(s)
      Yasushi Hirota、Takehiro Hiraoka、Tomoko Saito-Fujita、Tomoyuki Fujii、Yutaka Osuga
    • Organizer
      World Congress of Endometriosis 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Uterine hypoxia inducible factor contributes to blastocyst invasion by clearance of luminal epithelium at the site of blastocyst attachment2017

    • Author(s)
      Yasushi Hirota, Tomoko Saito-Fujita, Leona Matsumoto, Hirofumi HaraguchiMitsunori Matsuo, Takehiro Hiraoka, Shun Akaeda, Tomoki Tanaka, Norihiko Takeda, Yutaka Osuga, Tomoyuki Fujii
    • Organizer
      Society for the Study of Reproduction, 50th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Medical and Surgical Treatment in Adenomyosis2017

    • Author(s)
      Yasushi Hirota
    • Organizer
      18th APAGE Annual Congress 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生殖医学の最先端 不妊症治療におけるブレイクスルーを目指して 着床障害の分子機構の解明に基づく着床能の診断法と革新的治療技術の開発2017

    • Author(s)
      廣田泰
    • Organizer
      第69回日本産科婦人科学会学術講演会 シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低酸素誘導因子HIF2αによる子宮内膜への胚浸潤の調節2017

    • Author(s)
      松本 玲央奈, 廣田泰, 藤田知子, 伊賀上翔太, 田中智基, 平岡毅大, 松尾光徳, 原口広史, 赤枝俊, 武田憲彦, 大須賀穣, 藤井知行
    • Organizer
      第62回日本生殖医学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IL6-STAT3 signaling in adenomyosis2016

    • Author(s)
      Hirota Y.
    • Organizer
      Asian Conference of Endometriosis 2016
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] STAT3 promotes uterine regeneration in a mouse modelof decellularized uterine matrix transplantation2016

    • Author(s)
      Hirota Y.
    • Organizer
      Gordon Research Conference on Mammalian Reproduction
    • Place of Presentation
      Waterville Valley, NH, United States
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 黄体ホルモンによる子宮の胚受容能と着床の調節機構2016

    • Author(s)
      廣田泰
    • Organizer
      第5 回プロゲストーゲン研究会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 天然型プロゲステロンが着床に与える影響2016

    • Author(s)
      廣田泰
    • Organizer
      第3回最適な不妊治療を考える会
    • Place of Presentation
      東京
    • Year and Date
      2016-05-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] 研修ノート No99 流産のすべて2018

    • Author(s)
      廣田泰
    • Total Pages
      81
    • Publisher
      日本産婦人科医会
    • Related Report
      2017 Annual Research Report
  • [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

    • Related Report
      2018 Annual Research Report
  • [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

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東大産婦人科 廣田研究室

    • URL

      https://plaza.umin.ac.jp/tkyobgyn/recruit/laboratory/hirota.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 【プレスリリース】転写因子STAT3を介した子宮内膜の再構築と子宮の再生の仕組み

    • URL

      http://www.h.u-tokyo.ac.jp/vcms_lf/release_20160603-1.pdf

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2022-01-28  

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