Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in vitro: implications for treatment of ovarian hyperstimulation syndrome with dopamine receptor 2 agonists

Ferrero, H, Garcia-Pascual, C M, Gomez, R, Delgado-Rosas, F, Cauli, O, Simon, C, Gaytan, F, Pellicer, A,
Fertil Steril. May. 2014 doi: 10.1016/j.fertnstert.2014.01.031


OBJECTIVE: To ascertain whether vascular endothelial growth factor (VEGF) secretion by luteinized granulosa cells (GCs) is modulated by the dopaminergic system in a dose-dependent fashion and how this is related to the differential efficacy of dopamine receptor 2 (D2)-agonists (D2-ag) in preventing ovarian hyperstimulation syndrome (OHSS). DESIGN: The relationship between the dopaminergic system and VEGF secretion in luteinized GCs was evaluated. Archived human ovaries were immunostained to characterize D2 expression. SETTING: University affiliated infertility center. PATIENT(S): Premenopausal women and egg donors. INTERVENTION(S): Luteinized GCs were cultured with the D2-ag cabergoline. Human ovarian sections were immunostained for D2. MAIN OUTCOME MEASURE(S): The VEGF was measured by ELISA and D2 expression was evaluated by In-Cell ELISA. The D2 expression throughout the luteal phase was characterized by immunohistochemistry. RESULT(S): The VEGF secretion was decreased by the D2-ag in a dose-dependent fashion. The efficiency of this process was correlated with the amount of D2 expressed by luteinized GCs. A decrease in D2 expression in ovarian sections was observed during the late luteal phase. CONCLUSION(S): The efficacy of D2-ags in preventing OHSS might rely on their capacity to inhibit VEGF secretion by luteinized GCs. Because this capacity is dose-dependent, increasing the intraovarian concentration of D2-ags should be explored as a means of increasing the efficacy of these drugs in preventing OHSS.