The effect of hyperstimulation on vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX2) in the rat uterus in early pregnancy

Abstract

ABSTRACT Vascular permeability and angiogenesis are crucial events in the rodent and human uterus in early pregnancy and are regulated by vascular endothelial growth factor (VEGF) and prostaglandins liberated from arachidonic acid by cyclooxygenase 2 (COX2). These events coincide with the typical morphological features of the receptive uterus and are regulated by synchronized release of ovarian hormones (oestrogen and progesterone). However, administration of follicle stimulating hormone (FSH) and human chorionic gonadotropin (hCG), commonly used in assisted reproduction, affect the synchrony of the hormonal milieu, particularly by increasing oestrogen levels. This causes detrimental changes to the uterine morphology and affects vascular permeability at the site of implantation. In the present study, the expression of COX2 and VEGF was compared between control and hyperstimulated rat uteri during the peri-implantation period using immunohistochemistry and Western blot analysis. While in control pregnant rats COX2 and VEGF immunolocalization occurred in the luminal epithelial cells and stroma on consecutive days, strong immunolocalization of COX2 and VEGF occurred in the luminal epithelial cells but was inhibited in the stroma of the hyperstimulated rats. This appears to have resulted in the suppression of stromal decidualization and vascular permeability. Western blot analysis did not show any results. This may be due to low concentrations of the protein in the sample. Since vascular permeability and angiogenesis are critical to the process of implantation and are influenced by VEGF and COX2, disturbance of the pattern of these two proteins by hyperstimulation may contribute to the low implantation rate in IVF programes. immunohistochemistry and Western blot analysis. While in control pregnant rats COX2 and VEGF immunolocalization occurred in the luminal epithelial cells and stroma on consecutive days, strong immunolocalization of COX2 and VEGF occurred in the luminal epithelial cells but was inhibited in the stroma of the hyperstimulated rats. This appears to have resulted in the suppression of stromal decidualization and vascular permeability. Western blot analysis did not show any results. This may be due to low concentrations of the protein in the sample. Since vascular permeability and angiogenesis are critical to the process of implantation and are influenced by VEGF and COX2, disturbance of the pattern of these two proteins by hyperstimulation may contribute to the low implantation rate in IVF programes.