Platelet-Derived Growth Factor BB and DD and Angiopoietin1are altered in follicular fluid from Polycystic Ovary Syndrome patients.

ABRAMOVICH DALHIA; SCOTTI LEOPOLDINA; IRUSTA GRISELDA; PAZOS CAMILA; DE ZUÑIGA IGNACIO; BISIOLI CLAUDIO; PARBORELL FERNANDA; TESONE MARTA

Chicago

Congreso; ICE-ENDO 2014; 2014

Endocrine Society

Polycystic Ovary Syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age. Among other diverse features, PCOS is characterized by abnormalities in ovarian angiogenesis. While VEGF is the main angiogenic factor that promotes endothelial cell migration and proliferation, there are other angiogenic factor families involved in angiogenic process. Among these families are the Angiopoietin (ANGPT) and PDGF families, both involved in vessel stabilization and vascular permeability. It is known that follicular fluid (FF) levels and ovarian expression of VEGF are increased in PCOS patients. However, there are no studies analyzing other angiogenic factors in ovaries from PCOS women. Our hypothesis was that besides VEGF, other angiogenic factors are dysregulated in the ovaries from these patients, leading to altered angiogenesis and vascular permeability. Therefore, in this study we examined the levels of ANGPT1, ANGPT2, their soluble receptor TIE2 (sTIE2), PDGFBB and PDGFDD proteins in FF from PCOS (n=19) and control (n=27) patients undergoing assisted reproductive techniques. In addition, we analyzed the effect of FF from these patients on endothelial adherens and tight junction protein expression. We found a significant increase in the levels of ANGPT1 in PCOS patients (control: 201.1±23.1 pg/ml; PCOS: 516.4±81.8 pg/ml; p<0.0001) with no changes in the levels of the two soluble antagonists ANGPT2 and sTIE2. PDGFBB and PDGFDD were decreased in PCOS patients (PDGFBB: control: 1.29±0.15; PCOS: 0.81±0.05 arbitrary units; p<0.01) (PDGFDD: control: 2.37±0.14; PCOS: 1.94±0.07 arbitrary units; p<0.05). The levels of claudin 5 were significantly increased in endothelial cells incubated for 24h with PCOS follicular fluids compared to control FF (control: 2.05±0.13; PCOS: 3.50±0.52 arbitrary units; p<0.05). The levels of p-VE-cadherin, p-beta-catenin and ZO1 were no different in cells incubated with control and PCOS FF at any time point analyzed. These results suggest that the alterations observed in the ANGPTs and PDGFs levels may prevent VEGF-induced vascular leakage in the ovary at least in part by regulating endothelial cell junction proteins. Restoration of the levels of angiogenic factors may provide new insights to PCOS treatment and OHSS prevention in PCOS women.