Inhibition of platelet-derived growth factor (PDGF) receptor affects follicular development and ovarian proliferation, apoptosis a¬¬¬nd angiogenesis in prepubertal eCG-treated rats

PASCUALI N; SCOTTI L; ABRAMOVICH D; IRUSTA G; DI PIETRO M; BAS D; TESONE M; PARBORELL F

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Ireland; Año: 2015 vol. 412 p. 148 - 158

0303-7207

The platelet-derived growth factor (PDGF) system is crucial for blood vessel stability. In the presentstudy, we evaluated whether PDGFs play a critical intraovarian survival role in gonadotropindependentfolliculogenesis.We examined the effect of intrabursal administration of a selective plateletderivedgrowth factor receptor (PDGFR) inhibitor (AG1295) on follicular development, proliferation, apoptosisand blood vessel formation and stability in ovaries from rats treated with equine chorionic gonadotropin(eCG). The percentages of preantral follicles (PAFs) and early antral follicles (EAFs) were lower inAG1295-treated ovaries than in control ovaries (p < 0.01?0.05). The percentage of atretic follicles (AtrFs)increased in AG1295-treated ovaries compared to control (p < 0.05). The ovarian weight and estradiolconcentrations were lower in AG1295-treated ovaries than in the control group (p < 0.01 and p < 0.05,respectively), whereas progesterone concentrations did not change. AG1295 decreased the proliferationindex in EAFs (p < 0.05) and increased the percentage of nuclei positive for cleaved caspase-3 and apoptoticDNA fragmentation (p < 0.01?0.05). AG1295 increased the expression of Bax (p < 0.05) without changesin the expression of Bcl-2 protein. AG1295-treated ovaries increased the cleavage of caspase-8 (p < 0.05)and decreased AKT and BAD phosphorylation compared with control ovaries (p < 0.05). AG1295 causeda decrease not only in the endothelial cell area but also in the area of pericytes and vascular smoothmuscle cells (VSMCs) in the ovary (p < 0.05). Our findings suggest that the local inhibition of PDGFscauses an increase in ovarian apoptosis through an imbalance in the ratio of antiapoptotic to proapoptoticproteins, thus leading a larger number of follicles to atresia. PDGFs could exert their mechanism ofaction through an autocrine/paracrine effect on granulosa and theca cells mediated by PDGFRs. In conclusion,these data clearly indicate that the PDGF system is necessary for follicular development inducedby gonadotropins.