Effect of impaired glucose tolerance during pregnancy on the expression of VEGF receptors in human placenta

The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) receptors VEGFR-1, VEGFR-2 and VEGFR-3 in placentas from pregnancies complicated by altered glycaemia. Placentas from women with physiological pregnancies (Group 1), pregnancies complicated by minor degree of glucose intolerance (MDGI, Group 2) and by gestational diabetes mellitus (GDM) treated with insulin (Group 3) were collected. Immunohistochemistry, RT-PCR and western blot were employed to evaluate receptor expression. In the three study groups, VEGFR-1 immunoreactivity was detected in all the placental components. VEGFR-2 immunoreactivity was observed in the vessels of all the placentas from Groups 1 and 2, but only in some placentas of Group 3. VEGFR-3 reactivity was observed in all the components of Group 1; in Groups 2 and 3 reactivity was observed in some portions of the trophoblast or the whole trophoblast, and in the stroma. VEGFR-1 and VEGFR-2 mRNA levels in Groups 2 and 3 were significantly higher compared with Group 1, whereas those of VEGFR-3 were significantly lower. Receptor protein levels were significantly lower in Groups 2 and 3 compared with Group 1. These findings demonstrated dysregulation of expression of the three placental receptors, both in GDM and in MDGI.