Vascular disrupting effects of combretastatin A4 phosphate on murine endometriotic lesions

OBJECTIVE: To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions. DESIGN: Intravital microscopic, histologic, and immunohistochemical study. SETTING: University institute. ANIMAL(S): BALB/c mice. INTERVENTION(S): Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle. MAIN OUTCOME MEASURE(S): Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry. RESULT(S): All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls. CONCLUSION(S): This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.