Effect of pentoxifylline on vascular endothelial growth factor C and flk-1 expression on endometrial implants in the rat endometriosis model

• Published in: Fertility and sterility Vol. 93; no. 4; pp. 1316 - 1323
• Main Authors: Vlahos, Nikos F., M.D, Gregoriou, Odysseas, M.D, Deliveliotou, Aikaterini, M.D, Perrea, Despoina, Ph.D, Vlachos, Athanasios, M.D, Zhao, Yulian, Ph.D, Lai, Joseph, M.D, Creatsas, George, M.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2010
• Subjects: angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Disease Models, Animal; Endometriosis; Endometriosis - drug therapy; Endometriosis - metabolism; Endometriosis - surgery; Endometrium - drug effects; Endometrium - metabolism; Endometrium - transplantation; Female; flk-1; Infertility, Female - drug therapy; Infertility, Female - metabolism; Infertility, Female - surgery; Internal Medicine; Obstetrics and Gynecology; pentoxifylline; Pentoxifylline - pharmacology; Prospective Studies; Random Allocation; rat; Rats; Rats, Wistar; Transplants; Vascular Endothelial Growth Factor C - biosynthesis; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; VEGF; Endometriosis; pentoxifylline; flk-1; rat; angiogenesis; VEGF
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2008.10.056

Objective To investigate the effects of pentoxifylline, on vascular endothelial growth factor (VEGF)-C and flk-1 expression in the rat endometriosis model. Design Prospective, randomized, placebo-controlled study. Setting Academic institution. Animal(s) Twenty Wistar rats with surgically induced endometriosis. Intervention(s) Animals were evaluated after surgical induction of endometriosis and random allocation to a group that received pentoxifylline and a control group that received NaCl 0.9%, for 3 weeks. At the end of the treatment period the animals were killed and the implants evaluated macroscopically as well as by immunohistochemistry. Main Outcome Measure(s) Morphologic changes of the endometriotic implants; and evaluation of VEGF-C and flk-1 expression by a semiquantitative analysis (HSCORE) for the intensity of immunohistochemical reactivity. Result(s) A significant reduction was observed in the mean volume of the endometriotic implants per animal in the treatment group as compared with the control group. There was a significant reduction not only in the mean volume of implants per animal but also in the mean number of implants per animal after treatment. By immunohistochemical evaluation (HSCORE), there was a significant reduction in VEGF-C expression after treatment in all areas examined. A significant reduction of flk-1 expression was also noted in the glandular compartment after treatment but not in the epithelial surface or stroma. Conclusion(s) Pentoxifylline may cause suppression of endometriotic lesions by suppressing angiogenesis through VEGF-C and flk-1 expression.