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A role of endoplasmic reticulum stress in ovarian angiogenesis

Research Project

Project/Area Number 26462476
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

Harada Miyuki  東京大学, 医学部附属病院, 講師 (70451812)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords卵巣 / 血管新生 / 小胞体ストレス応答 / 血管内皮増殖因子 / 卵巣過剰刺激症候群
Outline of Final Research Achievements

Vascular endothelial growth factor A (VEGFA) is crucial for ovarian angiogenesis, but its excess production induces ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine whether endoplasmic reticulum (ER) stress regulates VEGFA expression in granulosa cells, and whether its activation is involved in OHSS development. The expression of the spliced form of X-box-binding protein 1 [XBP1(S)], induced by ER stress, in cumulus cells from OHSS patients was higher than non-OHSS patients. The ER stress inducer tunicamycin increased hCG-induced VEGFA production in human granulosa cells through the induction of XBP1(S), and pretreatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) abrogated the effect of tunicamycin. In OHSS model rats, TUDCA administration prevented the OHSS development. Our findings suggest ER stress upregulates hCG-induced VEGFA production in granulosa cells, indicating that ER stress might be involved in OHSS development.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 16 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (7 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] 大連医科大学附属第二病院(中国)

    • Related Report
      2016 Annual Research Report
  • [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] The Emerging Role of FOXL2 in Regulating the Transcriptional Activation Function of Estrogen Receptor β: An Insight into Ovarian Folliculogenesis2017

    • 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

    • DOI

      10.1177/1933719116651150

    • URL

      https://pure.teikyo.jp/en/publications/a510e310-ad12-45f7-ba18-ee76722a91a0

    • Related Report
      2016 Annual Research Report
    • 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

    • Related Report
      2016 Annual Research Report
    • 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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [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] Cyclic Stretch Augments Production of Neutrophil Chemokines, Matrix Metalloproteinases, and Activin A in Human Endometrial Stromal Cells.2015

    • Author(s)
      Izumi G, Koga K, Takamura M, Osuga Y.
    • Journal Title

      Am J Reprod Immunol

      Volume: epub Issue: 6 Pages: 501-506

    • DOI

      10.1111/aji.12359

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Laparoscopic excision of ovarian endometrioma does not exert a qualitative effect on ovarian function: insights from in vitro fertilization and single embryo transfer cycles.2015

    • Author(s)
      Harada M, Takahashi N, Hirata T, Koga K, Fujii T, Osuga Y
    • Journal Title

      J Assist Reprod Genet

      Volume: 32(5) Issue: 5 Pages: 685-9

    • DOI

      10.1007/s10815-015-0457-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Drospirenone induces decidualization in human eutopic endometrial stromal cells and reduces DNA synthesis of human endometriotic stromal cells.2015

    • Author(s)
      Miyashita, M., Koga, K., Izumi, G., Makabe, T., Hasegawa, A., Hirota, Y., Hirata, T., Harada, M., Fujii, T., Osuga, Y
    • Journal Title

      Fertility and Sterility

      Volume: 104 Issue: 1 Pages: 217-24

    • DOI

      10.1016/j.fertnstert.2015.03.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Four Cases of Postoperative Pneumothorax Among 2814 Consecutive Laparoscopic Gynecologic Surgeries: A Possible Correlation Between Postoperative Pneumothorax and Endometriosis.2015

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

      J Minim Invasive Gynecol

      Volume: 22 Issue: 6 Pages: 980-984

    • DOI

      10.1016/j.jmig.2015.04.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Evidence of the activation of unfolded protein response in granulosa and cumulus cells during follicular growth and maturation.2015

    • Author(s)
      Harada, M., Nose, E., Takahashi, N., Hirota, Y., Hirata, T., Yoshino, O., Koga, K., Fujii, T., Osuga, Y
    • Journal Title

      Gynecological Endocrinology

      Volume: 31 Issue: 10 Pages: 783-787

    • DOI

      10.3109/09513590.2015.1062862

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Simultaneous Detection and Evaluation of Four Subsets of CD4+ T Lymphocyte in Lesions and Peripheral Blood in Endometriosis.2015

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

      American Journal of Reproductive Immunology

      Volume: 74 Issue: 6 Pages: 480-486

    • DOI

      10.1111/aji.12426

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer2014

    • Author(s)
      Fujimoto A, Ichinose M, Harada M, Hirata T, Osuga Y, Fujii T.
    • Journal Title

      J Assist Reprod Genet

      Volume: 31 Issue: 9 Pages: 1189

    • DOI

      10.1007/s10815-014-0297-x

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-1β increases expression of tryptophan 2,3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells.2014

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

      Am J Reprod Immunol.

      Volume: 72 Issue: 5 Pages: 496-503

    • DOI

      10.1111/aji.12282

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study.2014

    • Author(s)
      Hirata T, Izumi G, Takamura M, Fujii T, Osuga Y.
    • Journal Title

      Gynecol Endocrinol

      Volume: 30 Issue: 10 Pages: 726729-726729

    • DOI

      10.3109/09513590.2014.926882

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dienogest reduces proliferation, aromatase expression and angiogenesis, and increases apoptosis in human endometriosis.2014

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

      Gynecol Endocrinol.

      Volume: 30 Issue: 9 Pages: 644-648

    • DOI

      10.3109/09513590.2014.911279

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone morphogenetic protein 7 increased vascular endothelial growth factor (VEGF)-a expression in human granulosa cells and VEGF receptor expression in endothelial cells.2014

    • Author(s)
      Akiyama I, Yoshino O et al.
    • Journal Title

      Reprod Sci.

      Volume: 21(4) Issue: 4 Pages: 477-82

    • DOI

      10.1177/1933719113503411

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 卵巣過剰刺激症候群における小胞体ストレス応答の役割と小胞体ストレス抑制剤の予防的効果2016

    • Author(s)
      高橋 望、原田 美由紀、廣田 泰、平池 修、泉 玄太郎、高村 将司、平田 哲也、甲賀 かをり、大須賀 穣、藤井 知行
    • Organizer
      第61回日本生殖医学学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 私はこうする:ART診療実践講座7 当科におけるラボ管理とリスク対策ーよりよい妊娠率と合併症の減少を目指してー2016

    • Author(s)
      大井なぎさ 原田美由紀 平田哲也 中澤明里 平野茉来 秋山育美 金谷真由子 山本直子 泉玄太郎 堤亮 大須賀穣 藤井知行
    • Organizer
      第61回日本生殖医学学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高齢不妊症患者に対する治療戦略としてのARTと子宮筋腫核出術とのコンビネーション療法:卵巣加齢の影響を最小限にするための戦略2016

    • Author(s)
      田邉良介、原田美由紀、大井なぎさ、平田哲也、泉玄太郎、高橋望、金谷真由子、山本直子、堤亮、廣田泰、甲賀かをり、平池修、大須賀穣、藤井知行
    • Organizer
      第61回日本生殖医学学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] Endoplasmic reticulum (ER) stress induces vascular endothelial growth factor (VEGF) production in granulosa cells: implications for a novel therapeutic approach for OHSS2016

    • Author(s)
      Takahashi N, Harada M, Hirota Y, Yoshino O, Urata Y, Izumi G, Takamura M, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y
    • Organizer
      68th Annual Congress of the Japan Society of Obstetrics and Gynwcology
    • Place of Presentation
      東京
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endoplasmic reticulum stress induces vascular endothelial growth factor production in granulosa cells: implications for a novel therapeutic approach for ovarian hyperstimulation syndrome2016

    • Author(s)
      Takahashi N, Harada M, Hirota Y, Yoshino O, Hiraike O, Fujii T, Osuga Y
    • Organizer
      98th The Endocrine Society's Annual Meeting
    • Place of Presentation
      ボストン(米国)
    • Year and Date
      2016-04-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endoplasmic reticulum stress induces VEGF production in granulosa cells: implications for a novel therapeutic approach for OHSS2016

    • Author(s)
      Takahashi N, Harada M, Hirota Y, Yoshino O, Hiraike O, Fujii T, Osuga Y
    • Organizer
      98thENDO
    • Place of Presentation
      ボストン(米国)
    • Year and Date
      2016-04-01
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Laparoscopic excision of ovarian endometrioma may exert quantitative but not qualitative effects on affected ovaries in IVF settings2014

    • Author(s)
      Harada M, Oi N, Hirata T, Koga K, Fujii T, Osuga Y
    • Organizer
      96th The Endocrine Society's Annual Meeting
    • Place of Presentation
      シカゴ(米国)
    • Year and Date
      2014-06-21 – 2014-06-24
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2022-02-16  

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