Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome.

Abstract

Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled ovarian stimulation treatment. This iatrogenic condition is potentially lethal and occurs in 0.3-5% of stimulated ovarian cycles. hCG exacerbates OHSS. The pathophysiology of OHSS is still unknown; therefore, treatment regimens are aimed at ameliorating symptoms. Prominent features of OHSS are an elevated risk of thromboembolism due to enhanced production of von Willebrand factor by endothelial cells and ascites, or pulmonary edema due to increased vascular permeability followed by third space fluid accumulation. Both of these sequelae can be evoked by vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF). High concentrations of VEGF/VPF have been demonstrated in ascitic fluid from patients with OHSS, but the source of VEGF/VPF in these patients remained unidentified. Here we report that the messenger ribonucleic acid expression of VEGF/VPF in human luteinized granulosa cells (GCs) is dose and time dependently enhanced by hCG in vitro. Furthermore, VEGF/VPF proteins are produced by GCs. Our results suggest that the effects of hCG on the development and course of OHSS may be mediated by the production of VEGF/VPF by GCs.

IL-6 Promotes FSH-Induced VEGF Expression Through JAK/STAT3 Signaling Pathway in Bovine Granulosa Cells

“…In addition to endothelial cells, VEGF gene and protein are also expressed in ovarian granulosa cells, granulosa-lutein cells, thecal cells and thecal-lutein cells [4-6]. It has been found that changes in VEGF expression and its distribution in the ovary are closely related to follicular development and ovulation [7-9]. …”

Role of Vascular Endothelial Cell Growth Factor in Ovarian Hyperstimulation Syndrome

“…In cultured bovine ovarian granulosa cells (GC), either LH or E2 can stimulate VEGF mRNA expression, but the effects of LH are more rapid (48). Cultured human GC respond to hCG with increased VEGF mRNA production (49); this leads us to speculate that in our patients there is a sequential action of the administered hormones (FSH, human menopausal gonadotropins, and hCG) to first directly stimulate VEGF production. This is followed by increased estrogen production that independently augments VEGF.…”

Management of ovarian hyperstimulation syndrome. Produced on behalf of the BFS Policy and Practice Committee

“…VEGF-A increases capillary permeability and promotes angiogenesis (Geva & Jaffe, 2000). HCG stimulates VEGF production in human granulosa cells and increases serum VEGF levels (Neulen et al, 1995;Pellicer et al, 1999). Serum VEGF levels were found to be higher in women during the course of OHSS compared to a control group without OHSS (Abramov et al, 1997).…”