• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Study for the etiology of polycystic ovary using a rat model

Research Project

Project/Area Number 16591676
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSapporo Medical University

Principal Investigator

ENDO Toshiaki  Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (90213595)

Co-Investigator(Kenkyū-buntansha) CHIBA Hideki  Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (00295346)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsandrogen / insulin resistance / polycystic ovary / follicle atresia / Fas Ligand / matrix metalloproteinase / adiponectin / claudin-5 / Zucker (fa / fa)ラット / 多嚢胞卵巣 / 閉鎖卵胞 / polycystic ovary syndrome / insulin resistance / testosterone / apoptosis / Fas / Fas Ligand / caspase 8 / MT1-MMP / polysyctic ovary syndrome / testosteorone / BMI / HOMA
Research Abstract

One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats, as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and F … More asL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis
Recently adiponectin has been suggested to play important role in insulin sensitivity. And insulin resistance has been attracted attention in reproductive function. But the expression of adiponectin in ovaries and adiponectin function in reproductive function are not fully understood. Ovaries of immature Zucker fa/fa rats showed significantly increased number of atretic follicles, number of total follicles and the percentage of atretic follicels/total follicles compared to lean rats. Serum adiponectin expression in fa/fa rats was significantly decreased as they became older. Adiponectin and its receptors are expressed in rat ovaries of granulosa cells, thaca cells and colupus luteums. Furthermore western blot and realtime RT-PCR analysis showed the expression of adiponectin and its receptors in ovaries were decreased under hyperinsulinemia condition like adipose tissue, liver and skeletal muscle. Overall our present data firstly provide the altered ovarian morphology and altered expression and regulation of adiponectin and its receptors in insulin resistant rat ovaries. Thus insulin resistant might closely related to reproductive dysfunction and low adiponectin profile also might be one one of the main causes of infertility and PCOS like condition in Zucker fatty rats.
We investigated the mechanism by which a GnRH agonist (GnRHa) affects ovarian vascularity, vascular permeability, and expression of the tight junction protein claudin-5 in a rat model of ovarian hyperstimulation syndrome (OHSS). Ovarian vascular density and vessel endothelial area (percent) were assessed by immunohistochemical analysis of the distribution of von Willebrand factor, whereas vascular permeability was evaluated based on leakage of Evans blue. High doses of PMSG and hCG significantly increased ovarian weight, vascular permeability, vascular density, and the vessel endothelial area and significantly reduced expression of claudin-5 protein and mRNA. All of these effects were significantly and dose-dependently inhibited by administration of GnRHa. This suggests that reduced expression of claudin-5 plays a crucial role in the increased ovarian vascular permeability seen in OHSS and that its expression can be modulated by GnRHa treatment. Indeed, preventing redistribution of tight junction proteins in endothelial cells and the resultant loss of endothelial barrier architecture might be the key to protecting patients against massive extravascular fluid accumulation in cases of OHSS. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (19 results)

All 2006 2005 2004

All Journal Article (19 results)

  • [Journal Article] PCOSの排卵障害ならびにインスリン抵抗性に関する病態研究 : シンポジウム(2)PCOSの病態生理と臨床2006

    • Author(s)
      遠藤俊明ほか
    • Journal Title

      日産婦誌 58・10

      Pages: 1620-1628

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The association between polycystic ovary syndrome and female-to-male transsexuals.2006

    • Author(s)
      Baba T, et al.
    • Journal Title

      Hum Reprod 22・4

      Pages: 1011-1016

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.2006

    • Author(s)
      Honnma H, et al.
    • Journal Title

      Apoptosis 11・9

      Pages: 1525-1533

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Hyperstimulation and a gonadotoropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-52006

    • Author(s)
      Kitajima Y, et al.
    • Journal Title

      Endocrinology 147・2

      Pages: 694-699

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells.2006

    • Author(s)
      Nagasawa K, et al.
    • Journal Title

      J Cell Physiol 208・1

      Pages: 123-132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus : Review Article.2006

    • Author(s)
      Endo T, et al.
    • Journal Title

      Reproductive Medicine and Biology 5・1

      Pages: 235-243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metallo- proteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.2006

    • Author(s)
      Honnma H, et al.
    • Journal Title

      Apoptosis 11(9)

      Pages: 1525-1533

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hyperstimulation and a gonadotoropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5.2006

    • Author(s)
      Kitajima Y, et al.
    • Journal Title

      Endocrinology 147(2)

      Pages: 694-699

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells.2006

    • Author(s)
      Nagasawa K, et al.
    • Journal Title

      J Cell Physiol 208(1)

      Pages: 123-132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus : Review Article.2006

    • Author(s)
      Endo T, et al.
    • Journal Title

      Reproductive Medicine and Biology 5(1)

      Pages: 235-243

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] PCOSの排卵障害ならびにインスリン抵抗性に関する病態研究 : シンポジウム(2)PCOSの病態生理と臨床2006

    • Author(s)
      遠藤俊明, 他
    • Journal Title

      日産婦誌 58・10

      Pages: 1620-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The association between polycyatic ovary syndrome and female-to-male transsexuals.2006

    • Author(s)
      Baba T, et al.
    • Journal Title

      Hum Reprod 22・4

      Pages: 1011-6

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hyperstimulation and a gonadotoropin releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-52006

    • Author(s)
      Kitajima Y, et al.
    • Journal Title

      Endocrinology 147・2

      Pages: 694-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5.2006

    • Author(s)
      Yoshimitus Kitajima
    • Journal Title

      Endocrinology 14・2

      Pages: 694-699

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Elevation of both cyclooxygenase-2 and prostaglandin E(2) receptor EP3 expression in rat placenta after uterine artery ischemia-reperfusion.2006

    • Author(s)
      Kiyohiro Yamazaki
    • Journal Title

      Placenta 27

      Pages: 395-401

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identical changes in Bax expression, but not Fas ligand expression, occur in structural luteolysis n gonadotropin releasing hormone agonist-and prolactin-treated superovulated rats.2005

    • Author(s)
      Toshiaki Endo
    • Journal Title

      Life Sciences 76・19

      Pages: 2159-2169

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identical changes in Bax expression, but not Fas ligand expression, occur in structural luteolysis in gonadotropin releasing hormone agonist-and prolactin-treatedsuperoyulated rats.2005

    • Author(s)
      Endo T, Kiya T, et al.
    • Journal Title

      Life Science 76・19

      Pages: 2159-2169

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 多嚢胞性卵巣症候群患者の血中adiponectinとインスリン抵抗性(HOMA指数), BMI, adnrogennについて2005

    • Author(s)
      遠藤俊明, 北島義盛, 他
    • Journal Title

      日産婦誌 57・2

      Pages: 661-661

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Low-molecular-weight dextran infusion is more effective for the treatment of hemo- concentrarion due to severe ovarian hyperstimulation syndrome human albumin infusion.2004

    • Author(s)
      Endo t, Kitajima Y, et al.
    • Journal Title

      Fertil Steril 82・15

      Pages: 1449-1451

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi