Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis

Abstract

Study Questio: NDoes the phytochemical compound resveratrol inhibit vascularization of endometriotic lesions? Summary Answer: Resveratrol suppresses the development of new microvessels in endometriotic lesions by inhibiting endothelial cell proliferation. What Is Known Already: 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.STUDY Design: , SIZE, DURATIONThis 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.MATERIAL, SETTING, METHODSPeritoneal 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. Main Results and the Role of Chance: 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.LIMITATIONS, REASONS FOR CAUTIONEndometriotic 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. Wider Implications of the Findings: 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. Study Funding/Competing Interest: (S)This work was supported by a grant of the 'Freunde des Universitä tsklinikums des Saarlandes'. The authors have no conflicts of interest to declare. © 2013 The Author.