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

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Author:
TONG Xiao-mei(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
ZHANG Song-ying(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
SONG Tao(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
XU Wei-hai(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
LIN Xiao-na(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
SHU Jing(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
LIU Liu(Department of Reproductive Medicine,Sir Run Run Shaw Hospital,Affilliated with School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China)
Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
Volume 121, Issue 23, 2008
DOI:
Key Word:
gonadotropin-releasing hormone antagonist;gonadotropin-releasing hormone agonist;ovarian hyperstimulation syndrome;vascular endothelial growth factor

Abstract´╝Ü Background Ovadan 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 tdals 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.Methods 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 fit-1 and KDR,were detected by reverse transcriptase-polymerase chain reaction and Western blotting.Results 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.Conclusion 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.

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