Effect of Vascular Endothelial Growth Factor Inhibition on Endometrial Implant Development in a Murine Model of Endometriosis

Analía Gabriela Ricci, Carla Noemí Olivares, Olivares CN, Mariela Andrea Bilotas, Mariela Bilotas, Gabriela Meresman, Gabriela Fabiana Meresman, Barañao RI, Rosa Inés Barañao
Reproductive sciences (Thousand Oaks, Calif.) · 2011 · vol. 18(7) , pp. 614–622 · doi:10.1177/1933719110395406 · PMID:21266664 · W2169855351
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-28 ⓘ

Bevacizumab, an anti-VEGF agent, inhibited endometriotic lesion development in mice by reducing cell proliferation, vascular density, and increasing apoptosis, while also lowering peritoneal VEGF levels.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-08 · read from full text ⓘ

This paper investigated whether inhibiting vascular endothelial growth factor (VEGF) activity with the anti-VEGF monoclonal antibody bevacizumab affects ectopic endometrial implant development in a murine model of endometriosis. Two-month-old female BALB/c mice received surgery to induce endometriotic-like lesions, then were treated with bevacizumab starting on post-surgery day 15 for 2 weeks; lesions were quantified after sacrifice and lesion biology assessed via immunohistochemistry (PCNA for proliferation, CD34 for vascular density, and TUNEL for apoptosis), alongside VEGF measurement in peritoneal fluid by ELISA. Bevacizumab significantly reduced endometriotic-like lesion development, decreased cell proliferation, reduced vascular density, increased apoptotic cell percentages, and lowered peritoneal fluid VEGF levels. The study’s key limitation is that it uses a mouse model with induced lesions rather than directly testing mechanisms in human disease. This paper is centrally about endometriosis — it tests VEGF inhibition (bevacizumab) on endometrial implant development in a murine endometriosis model.

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Abstract

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 endometriotic-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 endometriotic-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. Vascular endothelial growth factor levels were evaluated in the peritoneal fluid by enzyme-linked immunoassay (ELISA). Treatment with bevacizumab significantly inhibited endometriotic lesion development (P < .05). Consistently, bevacizumab significantly inhibited cell proliferation in lesions (P < .01), reduced vascular density (P < .001), as well as increased the apoptotic cell percentage (P < .001). In addition, bevacizumab reduced VEGF levels in peritoneal fluid of endometriosis-induced animals (P < .05). In conclusion, this study suggests a direct effect of bevacizumab on the reduction of endometrial implant growth and supports further research on VEGF inhibition as a novel therapeutic modality in endometriosis.
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Abstract

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 endometriotic-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 endometriotic-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. Vascular endothelial growth factor levels were evaluated in the peritoneal fluid by enzyme-linked immunoassay (ELISA). Treatment with bevacizumab significantly inhibited endometriotic lesion development (P <.05). Consistently, bevacizumab significantly inhibited cell proliferation in lesions (P <.01), reduced vascular density (P <.001), as well as increased the apoptotic cell percentage (P <.001). In addition, bevacizumab reduced VEGF levels in peritoneal fluid of endometriosis-induced animals (P < .05). In conclusion, this study suggests a direct effect of bevacizumab on the reduction of endometrial implant growth and supports further research on VEGF inhibition as a novel therapeutic modality in endometriosis. Similar content being viewed by others

References

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endometriosis

MeSH descriptors

Angiogenesis Inhibitors Antibodies, Monoclonal Endometriosis Endometriosis Vascular Endothelial Growth Factor A Angiogenesis Inhibitors Animals Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antigens, CD34 Ascitic Fluid Ascitic Fluid Ascitic Fluid Bevacizumab Cell Proliferation Cell Proliferation Disease Models, Animal Endometriosis Female In Situ Nick-End Labeling

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