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.

ABRAMOVICH DAHIA; IRUSTA, GRISELDA; PARBORELL FERNANDA; TESONE MARTA

FERTILITY AND STERILITY

ELSEVIER SCIENCE INC

Año: 2010 vol. 93 p. 1369 - 1377

0015-0282

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 kinaseinsert 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.