Estrogen and hypoxia regulate expression of vascular endothelial growth factor and its receptors in uterine cervix of mice, which are localized in multiple cells of the tissue in mice and human

Abstract

We have previously demonstrated the existence and profile of VEGF and its receptors, Flt‐1 and KDR, in the uterine cervix of rodents and deciphered the genome‐wide genes it regulates; and more recently examined some of VEGF's roles in uterine cervical remodeling. In the present study, we examined the effects of hypoxia and estrogen on the expression pattern of VEGF and its receptors, and mapped their cellular expression in the uterine cervix of mice and human. Ovariectomized mice were treated dose‐dependently with either 17β‐estradiol (E2) or cobalt chloride (CoCl2), to mimic hypoxia. Both human and mice sections were stained with H&E and protein expression of VEGF and its receptors were performed using confocal immunofluorescence. Also, mice tissues were analyzed for gene and protein expressions using real time PCR and Western blot, respectively. VEGF and its receptors were localized in epithelial and stromal cells in both species. VEGF and Flt‐1 expression were up‐regulated dose dependently by E2, while KDR was down‐regulated (p<0.05). VEGF and KDR were up‐regulated by 30 minutes post CoCl2 treatment, while Flt‐1 was up‐regulated at 1h post treatment. We conclude that VEGF and its receptors are present and variably expressed in the uterine cervix of women and mice; their expression in mice is altered by hypoxia and estrogen dose‐dependently. Funding: Office of students Research, Appalachian State.