Administration of moderate and high doses of gonadotropins to female rats increases ovarian vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression that is associated to vascular hyperpermeability

Convincing evidence supports the role of ovarian-origin vas-cular endothelial growth factor (VEGF) in inducing vascular per-meability (VP) and ascites associated with ovarian hyperstimu-lation syndrome (OHSS) in mammals, including humans. A cir-culatory dysfunction has been described in every woman treated with gonadotropins for in vitro fertilization. It is not known, however, whether the action of gonadotropins also includes up-regulation of the VEGF receptor-2 (VEGFR-2) and whether in-creased VP is also found when milder stimulation is used. Thus, we applied an OHSS animal model to answer these questions. Immature female rats were stimulated with saline (control group) or with high (10 IU of eCG 3 4 days 1 30 IU hCG, OHSS group) or mild (10 IU of eCG 1 10 IU of hCG, mild-stimulation group) doses of gonadotropins. The VP and the ex