Molecular basis in endometrial cell differentiation induced by progesterone

• Project/Area Number: 16H05469
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: Osuga Yutaka 東京大学, 医学部附属病院, 教授 (80260496)
• Co-Investigator(Kenkyū-buntansha): 廣田 泰 東京大学, 医学部附属病院, 講師 (40598653) ; 平池 修 東京大学, 医学部附属病院, 准教授 (20529060) ; 甲賀 かをり 東京大学, 医学部附属病院, 准教授 (10396723) ; 平田 哲也 東京大学, 医学部附属病院, 登録研究員 (30431860) ; 原田 美由紀 東京大学, 医学部附属病院, 講師 (70451812)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); 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: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: プロゲステロン / 着床 / 子宮 / 子宮腺筋症 / 子宮内膜 / リモデリング / 再生医療 / 胚浸潤 / 細胞増殖 / KRAS変異 / ゲノム / プロゲスチン / 黄体ホルモン / 子宮内膜症 / 妊娠 / 細胞老化 / マクロファージ / 子宮再生 / 脱細胞化 / STAT3 / ノックアウトマウス

Outline of Final Research Achievements

Uterine progesterone (P4) signaling has been investigated in this study. We found that stromal HIF2α acts on the detachment of the endometrial luminal epithelium from the stroma via hypoxia-related signals, which P4 does not affect (JCI 2018), and that P4 suppresses cell proliferation of the endometrial luminal epithelium and induces the fragmentation of epithelial cells and its trophoblast phagocytosis at the embryo attachment site. We also found that KRAS mutation in adenomyosis induces P4 resistance (Nat Commun 2019), and that P4 and STAT3 signaling is involved in the uterine remodeling (Endocrinology 2017, JCI Insight 2016).

Academic Significance and Societal Importance of the Research Achievements

本研究では、着床を可能にする胚受容能という視点でプロゲステロンの支配下にある着床の機構を明らかにし、子宮内環境と妊娠の科学的理解が可能になった。母体による初期胚発育に対する影響が明らかになったことで、不妊症の原因解明だけではなく、胎児発育不全や妊娠高血圧症候群などの妊娠中の合併症の解明、出生後の児生育との関連についての理解や生活習慣で起こる各種疾患の病因・病態の解明にまでつなげるための道筋ができた点で、学術的・社会的意義のある研究成果が得られたといえる。また、子宮腺筋症の薬物療法抵抗性の機序を明らかにすることができ、子宮腺筋症の新たな治療選択への基盤的知見が得られた点でも、社会的意義がある。

Research Products

• [Journal Article] A National Survey of Umbilical Endometriosis in Japan (2020)
  • Author(s): Hirata Tetsuya,Koga Kaori,Kitade Mari,Fukuda Shinya,Neriishi Kazuaki,Taniguchi Fuminori,Honda Ritsuo,Takazawa Naoko,Tanaka Toshiaki,Kurihara Masatoshi,Nakajima Jun,Horie Shigeo,Nakai Hidekatsu,Enomoto Takayuki,Mandai Masaki,Narahara Hisashi,Kitawaki Jo,Harada Tasuku,Katabuchi Hidetaka,Yoshimura Kotaro,Osuga Yutaka
  • Journal Title: Journal of Minimally Invasive Gynecology Volume: 27 Issue: 1 Pages: 80-87
  • DOI: 10.1016/j.jmig.2019.02.021
  • Peer Reviewed
• [Journal Article] Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Anti-Tumor Effect of Inhibition of DNA Damage Response Proteins, ATM and ATR, in Endometrial Cancer Cells (2019)
  • Author(s): Takeuchi Makoto、Tanikawa Michihiro、Nagasaka Kazunori、Oda Katsutoshi、Kawata Yoshiko、Oki Shinya、Agapiti Chuwa、Sone Kenbun、Miyagawa Yuko、Hiraike Haruko、Wada-Hiraike Osamu、Kuramoto Hiroyuki、Ayabe Takuya、Osuga Yutaka、Fujii Tomoyuki
  • Journal Title: Cancers Volume: 11 Issue: 12 Pages: 1913-1913
  • DOI: 10.3390/cancers11121913
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Accumulation of advanced glycation end products in follicles is associated with poor oocyte developmental competence (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Endometriosis Triggers Excessive Activation of Primordial Follicles via PI3K-PTEN-Akt-Foxo3 Pathway (2019)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A survey of public attitudes toward uterus transplantation, surrogacy, and adoption in Japan (2019)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Placental expression of lysophosphatidic acid receptors in normal pregnancy and preeclampsia (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] A Japanese nationwide survey on the cryopreservation of embryos, oocytes and ovarian tissue for cancer patients (2019)
  • Author(s): Sanada Yuko、Harada Miyuki、Kunitomi Chisato、Kanatani Mayuko、Izumi Gentaro、Hirata Tetsuya、Fujii Tomoyuki、Suzuki Nao、Morishige Ken‐ichirou、Aoki Daisuke、Irahara Minoru、Tsugawa Koichiro、Tanimoto Mitsune、Nishiyama Hiroyuki、Hosoi Hajime、Sugiyama Kazuhiko、Kawai Akira、Osuga Yutaka
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 45 Issue: 10 Pages: 2021-2028
  • DOI: 10.1111/jog.14073
  • Peer Reviewed / Open Access
• [Journal Article] Increased LIGHT leading to sFlt-1 elevation underlies the pathogenic link between hydatidiform mole and preeclampsia (2019)
  • Author(s): Iriyama Takayuki、Wang Guan、Yoshikawa Midori、Mimura Nobuko、Matsui Haruka、Sayama Seisuke、Kumasawa Keiichi、Nagamatsu Takeshi、Koga Kaori、Kotani Tomomi、Niimi Kaoru、Yamamoto Eiko、Kellems Rodney E.、Xia Yang、Osuga Yutaka、Fujii Tomoyuki
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 01017-01017
  • DOI: 10.1038/s41598-019-46660-4
  • Peer Reviewed / Open Access
• [Journal Article] Role of oxidative stress in follicular fluid on embryos of patients undergoing assisted reproductive technology treatment (2019)
  • 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
  • Peer Reviewed
• [Journal Article] Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Serum Brain-derived Neurotrophic Factor Levels Mirror Bone Mineral Density in Amenorrheic and Eumenorrheic Athletes. (2019)
  • Author(s): Nose S, Yoshino O, Nomoto K, Harada M, Dohi M, Kawahara T, Osuga Y, Fujii T, Saito S.
  • Journal Title: Int J Sports Med. Volume: 40(4) Issue: 04 Pages: 276-282
  • DOI: 10.1055/a-0835-6119
  • Peer Reviewed
• [Journal Article] Sphingosine 1 Phosphate (S1P) Increased IL-6 Expression and Cell Growth in Endometriotic Cells. (2019)
  • Author(s): Yoshino O, Yamada-Nomoto K, Kano K, Ono Y, Kobayashi M, Ito M, Yoneda S, Nakashima A, Shima T, Onda T, Osuga Y, Aoki J, Saito S.
  • Journal Title: Reprod Sci. Volume: 1933719119828112 Issue: 11 Pages: 1460-1467
  • DOI: 10.1177/1933719119828112
  • 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 ovary (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Mdm2-p53-SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] 薬物療法 漢方,GnRH製剤の使い方 経口剤レルゴリクスを含めて (2019)
  • Author(s): 大須賀穣
  • Journal Title: 臨床婦人科産科 Volume: 73 Pages: 959-964
• [Journal Article] GnRHアナログ製剤の種類と特徴 (2019)
  • Author(s): 大須賀穣
  • Journal Title: 産科と婦人科 Volume: 86 Pages: 6-12
• [Journal Article] Endoplasmic Reticulum Stress Activated by Androgen Enhances Apoptosis of Granulosa Cells via Induction of Death Receptor 5 in PCOS (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] A survey of public attitudes towards third-party reproduction in Japan in 2014 (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Nerve Injury-Induced Protein1 (Ninj1) in Endometriosis (2018)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HIF2α in the uterine stroma permits embryo invasion and luminal epithelium detachment (2018)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs (2018)
  • Author(s): Hirata Tetsuya、Koga Kaori、Johnson Todd A.、Morino Ryoko、Nakazono Kazuyuki、Kamitsuji Shigeo、Akita Masanori、Kawajiri Maiko、Kami Azusa、Hoshi Yuria、Tada Asami、Ishikawa Kenichi、Hine Maaya、Kobayashi Miki、Kurume Nami、Fujii Tomoyuki、Kamatani Naoyuki、Osuga Yutaka
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 8502-8502
  • DOI: 10.1038/s41598-018-25065-9
  • Peer Reviewed / Open Access
• [Journal Article] CD11c+ M1-like macrophages (MΦs) but not CD206+ M2-like MΦ are involved in folliculogenesis in mice ovary (2018)
  • Author(s): Ono Yosuke、Nagai Miwako、Yoshino Osamu、Koga Kaori、Nawaz Allah、Hatta Hideki、Nishizono Hirofumi、Izumi Gentaro、Nakashima Akitoshi、Imura Johji、Tobe Kazuyuki、Fujii Tomoyuki、Osuga Yutaka、Saito Shigeru
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 8171-8171
  • DOI: 10.1038/s41598-018-25837-3
  • Peer Reviewed / Open Access
• [Journal Article] Activation of Nrf2 might reduce oxidative stress in human granulosa cells (2018)
  • 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: 印刷中 Pages: 1-9
  • DOI: 10.1016/j.mce.2017.10.002
  • Peer Reviewed / Open Access
• [Journal Article] Adenomyosis and adverse perinatal outcomes: increased risk of second trimester miscarriage, preeclampsia, and placental malposition. (2017)
  • Author(s): Hashimoto A, Iriyama T, Sayama S, Nakayama T, Komatsu A, Miyauchi A, Nishii O, Nagamatsu T, Osuga Y, Fujii T1
  • Journal Title: J Mater Fetal Neonata Med Volume: 印刷中 Issue: 3 Pages: 364-369
  • DOI: 10.1080/14767058.2017.1285895
  • Peer Reviewed
• [Journal Article] ジエノゲストの子宮腺筋症患者における臨床評価 - 多施設共同ランダム化プラセボ対照二重盲検並行群間用量反応比較試験 - (2017)
  • Author(s): 大須賀穣, 渡邉学, 萩野篤司
  • Journal Title: 薬理と治療 Volume: 45 Pages: 907-920
  • Peer Reviewed
• [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 Fertility (2017)
  • 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
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autotaxin-lysophosphatidic acid-LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways (2017)
  • 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: 2146-2160
  • DOI: 10.15252/embj.201696290
  • 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 amenorrhea (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis (2017)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor (2017)
  • Author(s): Fujii Tatsuya、Nagamatsu Takeshi、Morita Kazuki、Schust Danny J.、Iriyama Takayuki、Komatsu Atsushi、Osuga Yutaka、Fujii Tomoyuki
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12455-12455
  • DOI: 10.1038/s41598-017-12685-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of the efficacy and safety of dienogest in the treatment of painful symptoms in patients with adenomyosis: a randomized, double-blind, multicenter, placebo-controlled study (2017)
  • Author(s): Osuga Yutaka、Fujimoto-Okabe Haruka、Hagino Atsushi
  • Journal Title: Fertil Steril Volume: 108 Issue: 4 Pages: 673-678
  • DOI: 10.1016/j.fertnstert.2017.07.021
  • Peer Reviewed
• [Journal Article] Long-term use of dienogest in the treatment of painful symptoms in adenomyosis (2017)
  • Author(s): Osuga Yutaka、Watanabe Manabu、Hagino Atsushi
  • Journal Title: J Obstet Gynaecol Res Volume: 43 Issue: 9 Pages: 1441-1448
  • DOI: 10.1111/jog.13406
  • Peer Reviewed
• [Journal Article] Development of endometrioma after cervical conization (2017)
  • Author(s): Takahashi Nozomi、Koga Kaori、Arakawa Ichiro、Harada Miyuki、Oda Katsutoshi、Kawana Kei、Fujii Tomoyuki、Osuga Yutaka
  • Journal Title: Gynecol Endocrinol Volume: 34 Issue: 4 Pages: 1-4
  • DOI: 10.1080/09513590.2017.1393660
  • Peer Reviewed
• [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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Emerging Role of FOXL2 in Regulating the Transcriptional Activation Function of Estrogen Receptor β: An Insight Into Ovarian Folliculogenesis. (2017)
  • Author(s): Hirano M, Wada-Hiraike O, Fu H, Akino N, Isono W, Sakurabashi A, Fukuda T, Morita Y, Tanikawa M, Miyamoto Y, Nishi Y, Yanase T, Harada M, Oishi H, Yano T, Koga K, Oda K, Kawana K, Fujii T, Osuga Y.
  • Journal Title: Reprod Sci Volume: 24 Issue: 1 Pages: 133-141
  • DOI: 10.1177/1933719116651150
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The assessment of myometrium perfusion in patients with uterine fibroid by arterial spin labeling MRI. (2016)
  • Author(s): Takahashi N, Yoshino O, Hiraike O, Maeda E, Nakamura M, Hori M, Harada M, Koga K, Saito S, Fujii T, Osuga Y.
  • Journal Title: Springerplus Volume: 5 Issue: 1 Pages: 1907-1907
  • DOI: 10.1186/s40064-016-3596-0
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assisted reproductive technology pregnancy complications are significantly associated with endometriosis severity before conception: a retrospective cohort study. (2016)
  • Author(s): Fujii T, Wada-Hiraike O, Nagamatsu T, Harada M, Hirata T, Koga K, Fujii T, Osuga Y.
  • Journal Title: Reprod Biol Endocrinol Volume: 14 Issue: 1 Pages: 73-73
  • DOI: 10.1186/s12958-016-0209-2
  • Peer Reviewed / Open Access
• [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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Usefulness of T2 star-weighted imaging in ovarian cysts and tumors. (2016)
  • Author(s): Takahashi N, Yoshino O, Maeda E, Naganawa S, Harada M, Koga K, Hiraike O, Nakamura M, Tabuchi T, Hori M, Saito S, Fujii T, Osuga Y.
  • Journal Title: J Obstet Gynaecol Res Volume: 42 Issue: 10 Pages: 1336-1342
  • DOI: 10.1111/jog.13056
  • Peer Reviewed
• [Journal Article] Where are oncofertility and fertility preservation treatments heading in 2016? (2016)
  • Author(s): Harada M, Osuga Y.
  • Journal Title: Future Oncol Volume: 12 Issue: 20 Pages: 2313-2321
  • DOI: 10.2217/fon-2016-0161
  • Peer Reviewed
• [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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 子宮筋腫の薬物治療Update (2019)
  • Author(s): 大須賀穣
  • Organizer: 第59回日本産科婦人科内視鏡学会学術講演会
  • Invited
• [Presentation] 生殖医療-近未来へのイノベーション- (2019)
  • Author(s): 大須賀穣
  • Organizer: 第71回日本産科婦人科学会学術講演会
  • Invited
• [Presentation] 稀少部位子宮内膜症診療ガイドラインの解説 (2018)
  • Author(s): 大須賀穣
  • Organizer: 第23回日本生殖内分泌学会学術集会
  • Invited
• [Presentation] STAT3: A Key Transcriptional Factor Not Only in Embryo Implantation but also in Endometrial Regeneration (2018)
  • Author(s): Yasushi Hirota
  • Organizer: Society for Reproductive Investigation, 65th Annual Scientific Meeting, Endometrium Satellite Meeting
  • Int'l Joint Research / Invited
• [Presentation] Levonorgestrel Inhibits Embryo Implantation by Downregulation of Uterine LIF Expression (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Diet and Supplements for Endometriosis (2017)
  • Author(s): Yutaka Osuga
  • Organizer: 6 th Asian Congress of Endometriosis
  • Int'l Joint Research / Invited
• [Presentation] Novel immune mechanism in the development of endometriosis (2017)
  • Author(s): Yutaka Osuga
  • Organizer: 19th World Congress on In Vitro Fertilization in conjunction with VI. Society of Reproductive Medicine and Surgery Congress
  • Int'l Joint Research / Invited
• [Presentation] Novel strategies for ART in patients with endometriosis, adenomyosis, and uterine fibroid. (2017)
  • Author(s): Yutaka Osuga
  • Organizer: The 11th Congress of the Pacific Society for Reproductive Medicine
  • Int'l Joint Research / Invited
• [Presentation] Current problems in infertile women associated with endometriosis. (2017)
  • Author(s): Yutaka Osuga
  • Organizer: 7th Congress of the Asia Pacific Initiative on Reproduction
  • Int'l Joint Research / Invited
• [Presentation] Results from a phase 2 study of Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, VS. placebo in women with endometriosis-associated pain. (2017)
  • Author(s): Yutaka Osuga
  • Organizer: World Congress of Endometriosis 2017
  • Int'l Joint Research / Invited
• [Presentation] Activated IL6-STAT3 pathway in adenomyosis (2017)
  • Author(s): Yasushi Hirota、Takehiro Hiraoka、Tomoko Saito-Fujita、Tomoyuki Fujii、Yutaka Osuga
  • Organizer: World Congress of Endometriosis 2017
  • Int'l Joint Research / Invited
• [Presentation] Uterine hypoxia inducible factor contributes to blastocyst invasion by clearance of luminal epithelium at the site of blastocyst attachment (2017)
  • 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
  • Int'l Joint Research
• [Presentation] Medical and Surgical Treatment in Adenomyosis (2017)
  • Author(s): Yasushi Hirota
  • Organizer: 18th APAGE Annual Congress 2017
  • Int'l Joint Research / Invited
• [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
• [Remarks] 【プレスリリース】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] 【プレスリリース】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