Effect of human chorionic gonadotropin (hCG) on expression of vascular endothelial growth factor a (VEGF-a) in human mid-secretory endometrial cells in three-dimensional primary culture.

ABSTRACT

Several lines of evidence suggest that human uterine endometrial cells can bind human chorionic gonadotropin (hCG) which, in turn, influences the physiology of implantation stage endometrium. Vascular endothelial growth factor (VEGF) appears to be a candidate mediator in this process. However, our knowledge about hCG action on VEGF in human endometrial cells is very thin. In the present study, we have examined microscopically hCG binding to dissociated human endometrial cells collected from mid-luteal phase and maintained in three-dimensional primary co-culture on rat-tail collagen type I biomatrix and examined the effect of different concentrations (0, 1, 10, 100 and 1000 IU/ML) of hCG on VEGF expression and secretion by endometrial cells maintained in the above system. We report that both cytokeratin positive epithelial cells as well as vimetin positive stromal cells from human mid luteal phase endometrium could bind hCG and that their number increased (P < 0.01) steadily with time. Administration of hCG enhanced (P < 0.05) immunoreactive VEGF protein expression in dose dependent manner in endometrial cells retrieved from mid-luteal phase of cycle, and co-cultured in a three-dimensional cell culture system, but with no marked change in VEGF secretion. Collectively, it appears that hCG influences VEGF protein synthesis in human midluteal phase endometrial cells, but has little effect on post-translational regulation and secretion. From physiological homeostasis point of view, it is likely that synthesis and secretion of VEGF exhibits a modular and factorial regulation to achieve a fine tuning of this potent vasotropic agent in receptive stage endometrium.