Effect of Vascular Endothelial Growth Factor inhibition on endometrial implant development in a murine model of endometriosis

RICCI A; OLIVARES C; BILOTAS M; MERESMAN GF; BARAÑAO RI

REPRODUCTIVE SCIENCES

SAGE PUBLICATIONS INC

Año: 2011 vol. 18 p. 614 - 622

1933-7191

The main factor involved in neovascularization of ectopic endometrial tissue in endometriosis is the vascular endothelial growth factor (VEGF), which is produced both by the endometrial implant and by peritoneal macrophages. On the other hand, bevacizumab is an antiangiogenic agent used in the treatment of different tumors, like colorectal, pulmonary, and recently mammary. We evaluated the effect of the inhibition of VEGF activity with bevacizumab (Avastin®) on ectopic endometrial growth in a murine model of endometriosis. Two months old female BALB/c mice had surgery performed to induce endometriosis-like lesions. Treatment with bevacizumab started on post-surgery day 15 and continued during 2 weeks. Then animals were sacrificed, peritoneal fluid was collected and endometriosis-like lesions were counted, measured and removed. Cell proliferation, vascular density, and apoptosis were assessed by immunohistochemistry for Proliferating Cell Nuclear Antigen (PCNA), immunohistochemistry for CD34, and Terminal Deoxynucleotidil Transferase-Mediated dUTP Nick End Labeling (TUNEL) respectively. VEGF levels were evaluated in the peritoneal fluid by enzyme-linked immunoassay (ELISA). Treatment with bevacizumab significantly inhibited endometriotic lesion development (p