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IMPLICATION OF ANGIOGENIC FACTORS IN FEMALE REPRODUCTIVE TRACT

Research Project

Project/Area Number 14207064
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

TAKETANI Yuji  The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (10114539)

Co-Investigator(Kenkyū-buntansha) YANO Tetsu  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (90251264)
FUJII Tomoyuki  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (40209010)
KUGU Koji  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (30322051)
MOMOEDA Mikio  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (50221627)
OSUGA Yutaka  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (80260496)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥53,040,000 (Direct Cost: ¥40,800,000、Indirect Cost: ¥12,240,000)
Fiscal Year 2005: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2004: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2003: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2002: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000)
Keywordsadiponectin / endometrium / endometriosis / implantation / receptor / AMPkinase / ミッドカイン / 子宮内膜症 / GnRHアナログ / BrdU取り込み / 腹腔内貯留液 / 卵胞液 / 血管新生 / 妊娠中毒症 / sVEGFR-1(sFlt-1) / IP-10 / 血管新生抑制薬 / マウス子宮内膜症モデル
Research Abstract

Adiponectin, a pleiotropic cytokine, exerts its effects via the specific receptors, Adipo R1 and Adipo R2. Whereas circulating adiponectin concentrations decrease in women with endometriosis and endometrial cancer, possible effects of adiponectin and the presence of the receptors in the endometrium have not been determined. In this study, we examined the expression of adiponectin receptors, Adipo R1 and Adipo R2 in the human endometrium, and assessed effects of adiponectin in the endometrial cells. Expression of Adipo R1 and Adipo R2 in the endometrial tissues was evaluated by real-time quantitative PCR, in situ hybridization, and Western blotting. The effects of adiponectin on phosphorylation of AMP-activate protein kinase (AMPK), a regulator of energy homeostasis, in cultured endometrial stromal cells (ESCs) and epithelial cells (EECs) were studied by Western blotting. The effects of adiponectin on IL-1b-induced secretion of IL-6,IL-8 and MCP-1 from cultured ESCs were determined using specific ELISAs. The expression of Adipo R1 and Adipo R2 was detected in the endometrium. The expression of both genes was increased in the mid-luteal phase, the period of embryo implantation. In situ hybridization revealed that both Adipo R1 and Adipo R2 appeared to be equally expressed in the epithelial cells and in the stromal cells. Adiponectin increased phosphorylation of AMPK in ESCs and EECs. Adiponectin decreased IL-1b-induced secretion of IL-6,IL-8 and MCP-1 from ESCs. These findings suggest that adiponectin exerts energy-homeostatic and anti-inflammatory effects in the endometrium, and these effects might be relevant to pathological and physiological endometrium-related events such as implantation and endometriosis.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (38 results)

All 2006 2005 2004 Other

All Journal Article (25 results) Publications (13 results)

  • [Journal Article] Mechanical stretch upregulates IGFBP-1 secretion from decidualized endometrial stromal cells.2006

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, Hirota Y, Hirata T, Morimoto C, Yano T, Taketani Y
    • Journal Title

      Am J Physiol Endocrinol Metab 290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanical stretch upregulates IGFBP-1 secretion from decidualized endometrial stromal cells.2006

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, hirata T, Morimura C, Yano T, Yano T, Taketani Y.
    • Journal Title

      Am J Physiol Endocrinol Metad 290

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanical stretch upregulates IGFBP-1 secretion from decidualized endometrial stromal cells.2006

    • Author(s)
      Harada M., Osuga Y., Takemura Y., Yoshino O., Koga K., Hirota Y., Hirata T., Morimoto C., Yano T., Taketani Y.
    • Journal Title

      Am J Physiol Endocrinol Metab 290

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Concentration of adiponectin in peritoneal fluid is decreased in women with endometriosis2005

    • Author(s)
      Takemura Y, Osuga Y, Harada M, Hirata T, Koga K, Yoshino O, Hirota Y, Morimoto C, Yano T, Taketani Y
    • Journal Title

      Am J Reprod Immunol 54

      Pages: 217-221

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Serum adiponectin concentrations are decreased in women with endometriosis2005

    • Author(s)
      Takemura Y, Osuga Y, Harada M, Hirata T, Koga K, Morimoto C, Hirota Y, Yoshino O, et al.
    • Journal Title

      Hum Reprod 20

      Pages: 3510-3513

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GnRH II as a possible cytostatic regulator in the development of endometriosis2005

    • Author(s)
      Morimoto C, Osuga Y, Yano T, Takemura Y, Harada M, Hirata T, Hirota Y, Yoshino O, Koga K, Kugu K, Taketani
    • Journal Title

      Hum Reprod 20

      Pages: 3212-3218

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Possible involvement of thrombin/protease-activated receptor I system in the pathogenesis of endometriosis2005

    • Author(s)
      Hirota Y, Osuga Y, Hirata T, Yoshino O, Koga K, Harada M, Morimoto C, Nose E, et al.
    • Journal Title

      J Clin Endocrinol Metab 90

      Pages: 3673-3679

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of protease-activated receptor 2 stimulates proliferation and interleukin(IL)-6 and IL-8 secretion of endometriotic stromal cells.2005

    • Author(s)
      Hirota Y, Osuga Y, Hirata T, Harada M, Morimoto C, Yoshino O, Koga K, Yano T, Tsutsumi O, Taketani Y
    • Journal Title

      Hum Reprod 20

      Pages: 3547-3553

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Concentration of adiponectin in peritoncalb.2005

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, hirata T, Morimura C, Yano T, Yano T, Taketani Y.
    • Journal Title

      Am J Physiol Immunol 54

      Pages: 217-221

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Serum sdipon concontrreasim2005

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, hirata T, Morimura C, Yano T, Yano T, Taketani Y.
    • Journal Title

      Hum Reprtod 20

      Pages: 3510-3513

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GnRH II as a possible cytostatio regulztor in the development of endometriosis.2005

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, hirata T, Morimura C, Yano T, Yano T, Taketani Y.
    • Journal Title

      Hum Reprtod 20

      Pages: 3212-3218

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Possible involvement of thrombin/protease-activated receptor I system in the pathogenesis of Endometriosis.2005

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, hirata T, Morimura C, Yano T, Yano T, Taketani Y.
    • Journal Title

      J Clin Endocrinol Metab 90

      Pages: 3673-3679

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromai ceiis.2005

    • Author(s)
      Harada M, Osuga Y, Takemura Y, Yoshino O, Koga K, hirata T, Morimura C, Yano T, Yano T, Taketani Y.
    • Journal Title

      Hun Reprod 20

      Pages: 3547-3553

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Concentration of adiponectin in peritoneal fluid is decreased in women with endometriosis2005

    • Author(s)
      Takemura Y., Osuga Y., Harada M., Hirata T., Koga K., Yashino O., Hirota Y., Morimoto C., Yano T., Taketani Y.
    • Journal Title

      Am J Reprod Immunol 54

      Pages: 217-221

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Serum adiponectin concentrations are decreased in women with endometriosis2005

    • Author(s)
      Takemura Y., Osuga Y., Harada M., Hirata T., Koga K., Morimoto C., Hirota Y., Yoshino O., Yano T., Taketani Y
    • Journal Title

      Hum Reprod 20

      Pages: 3510-3513

    • Related Report
      2005 Annual Research Report
  • [Journal Article] GnRH II as a possible cytostatic regulator in the development of endometriosis.2005

    • Author(s)
      Morimoto C., Osuga Y., Yano T., Takemura Y., Harada M., Hirata T., Hirota Y., Yoshino O., Koga K., Kugu K., Taketani Y
    • Journal Title

      Hum Reprod 20

      Pages: 3212-3218

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Possible involvement of thrombin/protease-activated receptor 1 system in the pathogenesis of endometriosis2005

    • Author(s)
      Hirota Y., Osuga Y., Hirata T., Yoshino O., Koga K., Harada M., Morinioto C., Nose E., Yano T., Tsutsumi O., Taketani Y
    • Journal Title

      J Clin Endocrinol Metab 90

      Pages: 3673-3679

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells.2005

    • Author(s)
      Hirota Y., Osuga Y., Hirata T., Harada M., Morimoto C., Yoshino O., Koga K., Yano T., Tsutsumi O., Taketani Y
    • Journal Title

      Hum Reprod 20

      Pages: 3547-3553

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Evidence for the presence of toll-like receptor 4 system in the human endometrium2005

    • Author(s)
      Hirata T, Osuga Y, Hirota Y, Koga K, Yoshino O, Harada M, Morimoto C, Yano T., Nishii O., Tsutsumi O., Taketani
    • Journal Title

      J Clin Endocrinol Metab 90・1

      Pages: 548-556

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanical stretch stimulates interleukin-8 production in endometrial stromal cells : possible implications in endometrium-related events2005

    • Author(s)
      Harada M, Osuga Y, Hirota Y, Koga K, Morimoto C, Hirata T, Yoshino O, Tsutsumi O., Yano T., Taketani Y
    • Journal Title

      J Clin Endocrinol Metab 90・2

      Pages: 1144-1148

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Evidence for the presence of protease-activated receptor 2 (PAR2) and its possible implication in remodeling of human endometrium2005

    • Author(s)
      Hirota Y, Osuga Y, Hirata T, Koga K, Yoshino O, Harada M, Morimoto C, Nose E., Yano T., Tsutsumi O., Taketani Y
    • Journal Title

      J Clin Endocrinol Metab (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women with endometriosis2004

    • Author(s)
      Harada M, Osuga Y, Hirata T, Hirota Y, Koga K, Yoshino O, Morimoto C, Fujiwara T, Momoeda M., Yano T., Tsutsumi O., Taketani Y
    • Journal Title

      Hum Reprod 19・10

      Pages: 2188-2191

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Possible pathophysiological roles of mitogen-activated protein kinases (MAPKs) in endometriosis2004

    • Author(s)
      Yoshino 0, Osuga Y, Hirota Y, Koga K, Hirata T, Harada M, Morimoto C, Yano T., Nishii O., Tsutsumi O., Taketani Y
    • Journal Title

      Am J Reprod Immunol 52・5

      Pages: 306-311

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen : an implication for the placental vascular development and the pathophysiology of preeclamosia2004

    • Author(s)
      Nagamatsu T, Fuili, Kusumi M, Zou L, Yamashita T, Osuga Y, Momoeda M, Kozuma S., Taketani Y
    • Journal Title

      Endocrinology 145・11

      Pages: 4838-4845

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 「研究成果報告書概要(和文)」より

    • Author(s)
      Y
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Koga K, Osuga Y, Yoshino O, Hirota Y, Ruimeng X, Hirata T, et al.: "Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia"J Clin Endocrinol Metab. 88・5. 2348-2358 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshino O, Osuga Y, Hirota Y, Koga K, Hirata T, Yano T, et al.: "Endometrial stromal cells undergoing decidualization down-regulate their properties to produce proinflammatory cytokines in response to interleukin-1 beta via reduced p38 mitogen-activated protein kinase phosphorylation"J Clin Endocrinol Metab. 88・5. 2236-2241 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirota Y, Osuga Y, Yoshino O, Koga K, Yano T, Hirata T, et al.: "Possible roles of thrombin-induced activation of protease-activated receptor 1 in human luteinized granulosa cells"J Clin Endocrinol Metab. 88・8. 3952-3957 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshino O, Osuga Y, Koga K, Hirota Y, Tsutsumi O, Yano T, et al.: "Concentrations of interferon-gamma-induced protein-10(IP-10), an antiangiogenic substance, are decreased in peritoneal fluid of women with advanced endometriosis"Am J Reprod Immunol. 50・1. 60-65 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshino O, Osuga Y, Koga K, Hirota Y, Yano T, Tsutsumi O, et al.: "Upregulation of interleukin-8 by hypoxia in human ovaries"Am J Reprod Immunol. 50・4. 286-290 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshino O, Osuga Y, Hirota Y, Koga K, Yano T, Tsutsumi O, et al.: "Akt as a possible intracellular mediator for decidualization in human endometrial stromal cells"Mol Hum Reprod. 9・5. 265-269 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujimoto A, Osuga Y, et al.: "Human Chorionic Gonadotropin Combined with Progesterone for Luteal Support Improves Pregnancy Rate in Patients with Low Late-Midluteal Estradiol Levels"J Assist Reprod Genet.. 19・12. 550-554 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujimoto A, Osuga Y, et al.: "Ovarian hyperstimulation syndrome complicated by peritonitis due to perforated appendicitis"Hum Reprod. 17・4. 966-967 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroi H, Osuga Y, et al.: "A case of estrogen-producing brenner tumor with a stromal component as a potential source for estrogen"Oncology. 63・2. 201-204 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osuga Y, Yano T, et al.: "Effects of gonadotropin-releasing hormone analog treatment on skin condition"Gynecol Endocrinol. 16・1. 57-61 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osuga Y, Koga K, et al.: "Role of laparoscopy in the treatment of endometriosis-associated infertility"Gynecol Obstet Invest. 53・Suppl 1. 33-39 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Xu J, Osuga Y, et al.: "Bisphenol A induces apoptosis and G2-to-M arrest of ovarian granulosa cells"Biochem Biophys Res Commun. 292・2. 456-462 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osuga Y, Kaori Koga, et al.: "Local regulators of the human ovary in associated reproductive technology (ART) in Recent Research in Development and Endocrinology"Trans Research Network. 349-357 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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