IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Metformin Treatment Decreases Ovarian VEGF and Angiopoietin1 Levels, Improves Follicular Development and Decreases Cyst Formation in a Rat Model of Polycystic Ovary Syndrome
Autor/es:
ABRAMOVICH D., SCOTTI L., IRUSTA G., PAZOS C., DE ZUÑIGA I., BISIOLI C., PARBORELL F., TESONE M
Reunión:
Congreso; 16th International Congress of Endocrinology & the Endocrine Society?s 96th Annual Meeting & Expo; 2014
Resumen:
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