Intrabursal injection of vascular endothelial growth factor trap in eCG-treated prepubertal rats inhibits proliferation and increases apoptosis of follicular cells involving the PI3K/AKT signaling pathway

Objective: To investigate the effects of local inhibition of vascular endothelial growth factor A (VEGFA) on proliferation and apoptosis of follicular cells in rat ovaries. To analyze the role of the PI3K/AKT signaling pathway on VEGFA effects. Design: Experimental study. Setting: Research laboratory. Animal(s): Female Sprague Dawley rats, 21 days old, treated with equine chorionic gonadotropin (eCG). Main Outcome Measure(s): Follicular cell proliferation, apoptosis, and activation of the PI3K/AKT signaling pathway after intrabursal injection of a VEGFA inhibitor. Result(s): Inhibition of VEGFA leads to a decrease in the expression of the proliferation marker proliferating cell nuclear antigen (PCNA) in theca and granulosa cells (GC) and an increase in the activation of caspase 3 in antral follicles. Furthermore, we observed a decrease in the phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) and its target Bcl2 antagonist of cell death (BAD). No differences were found in the levels of kinase insert domain receptor (KDR) protein or in endothelial cell density. Conclusion(s): The VEGFA prevents apoptosis and stimulates proliferation of follicular cells, regulating follicular growth and development. The PI3K/AKT signaling pathway is one of the pathways involved in this mechanism. Therefore. VEGFA has a role as an antiapoptotic and proliferative factor in follicular cells from the rat ovary. (Fertil Steril (R) 2010;93:1369-77. (C)2010 by American Society for Reproductive Medicine.)