Inhibition of cyclooxygenase (COX)-2 suppresses the recruitment of endothelial progenitor cells in the microvasculature of endometriotic lesions.

The incorporation of endothelial progenitor cells (EPCs) into newly developing blood vessels contributes to the vascularization of endometriotic lesions. here, we analyzed whether cyclooxygenase (COX)-2 signaling regulates this vasculogenic process. Endometriotic lesions were surgically induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein (GFP)) 287 Sato mice. The animals received β-estradiol 17-valerate once a week and were daily treated with the selective COX-2 inhibitor parecoxib (25 mg/kg) or vehicle (control) over 7 and 28 days. Analyses involved the determination of lesion growth, cyst formation, homing of GFP(+)/Tie2(+) EPCs, numbers of circulating EPCs, vascularization, cell proliferation, apoptosis, and immune cell infiltration by means of high-resolution ultrasound imaging, caliper measurements, flow cytometry, histology, and immunohistochemistry. In parecoxib-treated mice, blood circulating EPCs were higher but numbers of recruited EPCs in endometriotic lesions were significantly lower when compared to controls. This was associated with an impaired early vascularization and stromal tissue growth as well as reduced glandular secretory activity of the lesions. Parecoxib-treated lesions further contained less proliferating and more apoptotic cells and exhibited lower numbers of infiltrating macrophages and neutrophilic granulocytes. These findings demonstrate that the inhibition of COX-2 suppresses vasculogenesis in endometriotic lesions. This may contribute to an impaired lesion vascularization and growth.