Localization and control of expression of VEGF-A and the VEGFR-2 receptor in fetal sheep intestines

We studied expression of vascular endothelial growth factor A (VEGF-A) and its main receptor, VEGFR-2, in the small intestine from five groups of fetal sheep (each n = 5): 1) preterm controls, 2) term controls, 3) preterm animals where the fetus was infused with cortisol, or 4) saline, and 5) term animals where adrenalectomy had been performed preterm. The main transcript expressed in fetal small intestine was VEGF-A(165). Comparing term with preterm animals, there were significantly higher levels of expression of VEGF-A protein (p = 0.005). Levels of VEGF-A protein expression were lower in term adrenalectomized animals (p = 0.01) and were higher in preterm animals infused with cortisol (p = 0.01), compared with their respective control groups. Immunohistochemistry demonstrated strongest expression of VEGF-A protein in the epithelial cells and lamina propria of the villi. Intestinal expression of mRNA encoding the VEGFR-2 receptor did not significantly vary with gestational age. In situ hybridization localized VEGFR-2 to the lamina propria of the villous core and receptor autoradiography using 1251 VEGF-A demonstrated binding in the same site. These data show that intestinal VEGF-A is up-regulated with advancing gestation in a glueocorticoid-dependent manner-novel findings consistent with a role for VEGF-A stimulated angiogenesis in preparing the fetal gut for birth.