Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia

ObjectiveTo investigate whether the structure or regulation of the growth of endometrial blood vessels might be abnormal in women with idiopathic menorrhagia (IM). Perturbation of angiogenesis is associated with IM.DesignProspective, clinical study.SettingDepartment of gynecology at a university hospital.Patient(s)Twenty-four patients with IM, and 18 women with eumenorrhea.Intervention(s)Endometrial biopsy samples underwent immunohistochemical staining for CD34, CD31, von Willebrand factor, vascular endothelial growth factor (VEGF)-A, and VEGF receptors 1 and 2.Main Outcome Measure(s)Differences in immunostaining for these markers by computer-assisted stereological analysis.Result(s)Endometrial vessels in patients and controls manifested focal discontinuities, or gaps, in endothelial staining for CD34, CD31, and von Willebrand factor. Electron and confocal microscopy revealed that perivascular cells, probably pericytes, covered these gaps in the vessel wall. The relative size of the gaps was significantly greater in patients with IM than in controls. Vessel circumference was also larger, and more vessels were positive for VEGF-A and for VEGF receptors 1 and 2, in patients than in controls. Gap size was significantly correlated with the number of vessels expressing VEGF-A or VEGF receptor 1.Conclusion(s)Endometrial blood vessels possess a discrete morphology that is characterized by endothelial gaps, and these gaps [1] are more pronounced in women with IM, [2] are related to overexpression of VEGF-A and VEGF receptor 1, and [3] might contribute to IM, e.g., by destablizing vessels.