Vascular endothelial growth factor expression in cycling human endometrium

Abstract

To determine the spatial distribution of vascular endothelial growth factor protein in human endometrium and to assess temporal fluctuations in vascular endothelial growth factor gene expression and variant isoform production by stromal and epithelial cells during the menstrual cycle. Prospective study design. Early proliferative endometrial biopsies were obtained from women undergoing gynecologic surgery for benign conditions; secretory stage biopsies were obtained from patients undergoing routine infertility investigations without evidence of luteal insufficiency. Immunohistochemical detection of vascular endothelial growth factor protein in endometrial biopsies, analyses of vascular endothelial growth factor RNA expression, and isoform production in intact endometrium and isolated endometrial stromal and epithelial cells. Strong vascular endothelial growth factor immunoreactivity was detected in the glandular epithelial cells of the secretory endometrium with no discernible immunoreactivity in stroma cells. The proliferative endometrium demonstrated prominent glandular immunoreactivity and faint, inconsistent stromal cell immunoreactivity. Preincubation of the antibody with excess cognate peptide abolished all immunoreactivity. A threefold to sixfold increase in vascular endothelial growth factor messenger RNA expression occurs in secretory versus proliferative endometrial samples. Endometrial stromal and epithelial cell isolates from both phases of the menstrual cycle express VEGF121, VEGF165, and VEGF189 isoforms, however, vascular endothelial growth factor variant 206 was not detected. Expression of vascular endothelial growth factor in the endometrium throughout the menstrual cycle suggests that vascular endothelial growth factor may promote the vascular growth, maintenance, and hyperpermeability required for adequate receptivity in the cycling human endometrium.