Novel pathophysiological role of PDGF-B in OHSS, an ovarian syndrome with vascular hyperpermeability and ascites.¬¬¬¬¬¬

PASCUALI NATALIA; SCOTTI LEOPOLDINA; OUBIÑA, GONZALO; DE ZUÑIGA IGNACIO; TESONE, MARTA; BUSSO DOLORES; ABRAMOVICH DALHIA; PARBORELL FERNANDA

Congreso; International Vascular Biology Meeting; 2018

Ovarian hyperstimulation syndrome is a life-threatening iatrogenic pathology/complication/disease resulting from vasoactive products released by stimulated ovaries. It affects 5-10% of women under hormone stimulation for assisted reproductive techniques. It produces fluid shift from the vascular compartment to the third space due to capillary hyperpermeability, leading to ascites and, if not properly managed, haemoconcentration and renal failure. The crux is an equilibrium between proangiogenic and antiangiogenic factors present in follicular fluid (FF), with VEGF as key mediator of this syndrome; however, the role of other angiogenic factors remains unknown. Our aim was to characterize the composition and angiogenic potential of FF from patients at risk of developing OHSS and to study the effect of PDGF-B ovarian administration in a rat OHSS model.We assessed protein levels of S1P and PDGF ligands and receptors by Western Blot, as well as the lipoprotein profile by FPLC, in FF from control and OHSS patients. We also studied the angiogenic effect of these FF on the chorioallantoic membrane (CAM) of quail embryos. Finally, we investigated the effect of ovarian administration of recombinant PDGF-B in a rat model of OHSS.OHSS FF have lower levels of PDGF-B, PDGF-D and S1P than control FF. HDL particles from OHSS FF are larger, filled with more cholesterol and less ApoA-I than control ones. CAMs stimulated with OHSS FF present vasculature with less peri-endothelial coverage than control FF-stimulated ones, which is partially restored by PDGF addition to OHSS FF (assessed by α-SMA immunofluorescence). Ovarian blood vessels from the OHSS rat model are highly permeable, have deficient perivascular coverage and decreased levels of junction proteins like N-cadherin and Claudin-5. Local injection of PDGF-B restored these parameters to control values. Our findings suggest that decreased PDGF-B is involved in OHSS pathogenesis. Elucidating the mechanisms by which PDGF regulates vasculature in OHSS could help identify new therapeutic targets for diseases with aberrant vascular leakage.