Effect of antiangiogenic treatment on peritoneal endometriosis-associated nerve fibers

Novella-Maestre, E, Herraiz, S, Vila-Vives, J M, Carda, C, Ruiz-Sauri, A, Pellicer, A,
Fertil Steril. Nov. 2012 doi: 10.1016/j.fertnstert.2012.07.1103


OBJECTIVE: To investigate the effect of antiangiogenic treatment on experimental endometriotic lesion nerve fibers. DESIGN: Heterologous mouse model of endometriosis. SETTING: University Institute IVI, University Hospital La Fe. ANIMAL(S): Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4). INTERVENTION(S): Endometrium fragments stuck in the peritoneum of 5-week-old female nude mice treated with vehicle (n = 8) and antiangiogenic agent cabergoline (n = 8; Cb(2,) 0.05 mg/kg/day) for 14 days. MAIN OUTCOME MEASURE(S): Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (alphaSMA) for evaluating the number of immature blood vessels (IBV) and microvascular density (MVD); immunochemical analysis of protein-gene product 9.5 (PGP 9.5) to assess nerve fibers density (NFD), and blue toluidine staining to confirm presence of mast cells and macrophages in endometriotic lesions. RESULT(S): All the results were quantified by morphometric techniques. The IBV, NFD, and number of macrophages and mast cells were statistically significantly decreased in the Cb2-treated group when compared with controls. CONCLUSION(S): Antiangiogenic treatment statistically significantly diminishes new blood vessel formation after macrophage, mast cell, and nerve fiber reduction, providing a rationale to test antiangiogenic agents as a novel therapeutic approach to severe pelvic pain associated with human peritoneal endometriosis.