Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in an ovarian hyperstimulation syndrome (OHSS) animal model: implications for treatment of OHSS with dopamine receptor 2 agonists

Objective To explore whether a dopamine receptor 2 agonist (D2-ag) can prevent ovarian hyperstimulation syndrome (OHSS) in a rat model by decreasing ovarian vascular endothelial growth factor (VEGF) production. Design Experimental study in an OHSS animal model. Setting University-affiliated infertility center. Patient(s) Immature Wistar rats. Intervention(s) Immature rats were stimulated with gonadotropins to mimic OHSS and treated with a D2-ag and/or D2-antagonists (D2-ant). Vascular permeability (VP) was measured at the endpoint, and ovaries were collected to assess the effects of these drugs on VEGF production. Main Outcome Measure(s) VP was estimated by measuring the peritoneal extravasation of a previously injected dye. Ovarian VEGF mRNA expression and VEGF protein levels were assessed by quantitative real-time PCR and Western blots, respectively. Result(s) The D2-ag exerted a reduction in VP that was associated with a drastic decrease in VEGF protein production in OHSS rat ovaries. The effects of this D2-ag on VP and VEGF protein levels were partially reversed by concomitant administration of a D2-ant. Ovarian VEGF mRNA expression levels were unaffected by these drugs in OHSS rats. Conclusion(s) D2-ags prevent increased VP in OHSS rats by decreasing ovarian VEGF production, very likely through a D2-mediated post-transcriptional mechanism. Given the dose-dependent inhibitory effect of D2-ags on ovarian VEGF production reported herein, we infer that current OHSS therapies used in humans may be improved by increasing the intraovarian concentration of D2-ags in these patients.