title: Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis.
abstract: OBJECTIVE
  Does the phytochemical compound resveratrol inhibit vascularization of endometriotic lesions?
  
  
  CONCLUSIONS
  Resveratrol suppresses the development of new microvessels in endometriotic lesions by inhibiting endothelial cell proliferation.
  
  
  BACKGROUND
  Establishment and progression of endometriosis is crucially dependent on angiogenesis. Resveratrol is a pleiotropic agent, which dose-dependently suppresses the development of new blood vessels.
  
  
  METHODS
  This was a randomized study in a mouse model of endometriosis. Twenty female BALB/c mice with surgically induced endometriosis were treated with resveratrol (40 mg/kg/day, n = 10) or vehicle (n = 10) for 4 weeks.
  Peritoneal and mesenteric endometriotic lesions were surgically induced by uterine tissue transplantation into the abdominal cavity of BALB/c mice. The animals were daily treated with resveratrol (40 mg/kg) or vehicle by oral gavage. Lesion growth, vascularization, apoptosis and cell proliferation were subsequently analyzed by means of high-resolution ultrasound imaging, caliper measurements, histology and immunohistochemistry throughout an observation period of 4 weeks.
  
  
  RESULTS
  Resveratrol inhibited angiogenesis in peritoneal and mesenteric endometriotic lesions, as indicated by a significantly reduced microvessel density when compared with controls. Additional immunohistochemical analyses revealed that this was caused by a decreased proliferating activity of CD31-positive endothelial cells in the newly developing microvasculature of the lesions. In line with these findings, lesions in resveratrol-treated mice exhibited a reduced growth rate and a smaller final size than controls. This was associated with lower numbers of proliferating cell nuclear antigen- and Ki67-positive stromal and glandular cells. Apoptotic cells were not detectable in either group. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate controls. Statistical significance was accepted for a value of P < 0.05.
  
  
  CONCLUSIONS
  Endometriotic lesions were surgically induced by uterine tissue transplantation without the use of pathological endometriotic tissue of human origin. Therefore, the results obtained in this mouse model may not fully correlate to human patients with endometriosis.
  
  
  CONCLUSIONS
  Resveratrol is a potent inhibitor of vascularization in endometriotic lesions. This, most probably, causes the suppression of lesion growth. Accordingly, resveratrol represents a promising candidate therapy for future phytochemical treatment of endometriosis.
  
  
  BACKGROUND
  This work was supported by a grant of the 'Freunde des Universitätsklinikums des Saarlandes'. The authors have no conflicts of interest to declare.
authors: Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar D66421, Germany. jeannette.rudzitis-auth@uks.eu
authors: J
authors: J
authors: Rudzitis-Auth
authors: M D
authors: MD
authors: Menger
authors: M W
authors: MW
authors: Laschke
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy*; D004717:Endometrium / Q000187:drug effects; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013267:Stilbenes; D000077185:Resveratrol