Platelet-derived growth factor B restores vascular barrier integrity and diminishes permeability in ovarian hyperstimulation syndrome

Abstract

Although advances in the prediction and management of OHSS have been introduced, complete prevention has not been possible yet. Previously, we and other authors have shown that VEGF, ANGPTs and S1P are involved in OHSS etiology. In addition, we have demonstrated that ovarian protein levels of PDGF ligands -B and -D decrease in an OHSS rat model, whilst PDGFR-β and ANGPT2 remain unchanged. In the present work, we delved into the role of PDGF-B in OHSS by evaluating ligand levels in follicular fluid (FF) from women at risk of developing OHSS and by using an animal model that develops OHSS in immature rats. We demonstrated that PDGF-B and PDGF-D are lower in FF from women at risk of developing OHSS compared to control patients. In the OHSS rat model, PDGF-B (0.5 µg/ovary) administration decreased ovarian weight, reduced serum progesterone and lowered the percentage of cysts vs untreated OHSS rats, but had no effect on the proportion of follicles or corpora lutea. PDGF-B treatment also restored the expression of StAR and P450scc to control levels. In addition, PDGF-B increased the peri-endothelial cell area in CL and cystic structures and reduced vascular permeability compared to untreated OHSS ovaries. Lastly, PDGF-B restored the levels of junction proteins claudin-5, occludin and β-catenin to control values, while increasing the extracellular deposition of collagen IV surrounding ovarian vasculature. In conclusion, our findings indicate that PDGF-B could be another crucial mediator in the onset and development of OHSS, leading to novel prediction markers and therapeutic strategies.