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.


METHODS
Experimental study.


METHODS
Research laboratory.


METHODS
Female Sprague Dawley rats, 21 days old, treated with equine chorionic gonadotropin (eCG).


METHODS
Follicular cell proliferation, apoptosis, and activation of the PI3K/AKT signaling pathway after intrabursal injection of a VEGFA inhibitor.


RESULTS
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.


CONCLUSIONS
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.
Abramovich
Dalhia
D
Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
Irusta
Griselda
G
Parborell
Fernanda
F
Tesone
Marta
M