Effects of gonadotropin-releasing hormone antagonists on the expression of vascular endothelial growth factor and its receptors in a rat model of ovarian hyperstimulation syndrome

Abstract

Ovarian hyperstimulation syndrome (OHSS) is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists (GnRHanta) are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor (VEGF) and its receptors in a rat model of OHSS. An immature early OHSS rat model was established. Three ovarian stimulation protocols were used: pregnant mare serum gonadotropin/human chorionic gonadotropin (hCG) alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists (GnRHa). Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including flt-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.