Platelet‐derived growth factor BB and DD and angiopoietin1 are altered in follicular fluid from polycystic ovary syndrome patients

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, and is characterized by abnormalities in ovarian angiogenesis, among other features. Consistent with this association, follicular fluid (FF) concentration and ovarian expression of vascular endothelial growth factor (VEGF) are increased in PCOS patients. In this study, we examined the protein levels of platelet-derived growth factor (PDGF) BB and DD (PDGFBB and PDGFDD), angiopoietin 1 and 2 (ANGPT1 and ANGPT2), and their soluble receptor sTIE2 in FF from PCOS and control patients undergoing assisted reproductive techniques. We also analyzed the effect of FF from PCOS and control patients on tight and adherens junction protein expression in an endothelial cell line. PDGFBB and PDGFDD were significantly lower whereas ANGPT1 concentration was significantly higher in FF from PCOS patients than from control patients. No changes were found in the concentration of ANGPT2 or sTIE2. Expression of claudin-5 was significantly increased in endothelial cells incubated for 24 hr in the presence of FF from PCOS versus from control patients, while vascular-endothelial cadherin, β-catenin, and zonula occludens 1 expression were unchanged. The changes observed in the levels of PDGF isoforms and ANGPT1 may prevent VEGF-induced vascular permeability in the PCOS ovary by regulating endothelial-cell-junction protein levels. Restoring the levels of angiogenic factors may provide new insights into PCOS treatment and the prevention of ovarian hyperstimulation syndrome in affected women.

Tankyrase inhibition regulates corpus luteum development and luteal function in gonadotropin‐treated rats

“…VEGF is the main initiator of angiogenesis, and acts by stimulating endothelial cell proliferation. Establishing a mature vascular network, however, requires the coordinated action of many additional factors, including Angiopoietins 1 and 2, which act via the tyrosine kinase receptor, Tie‐2 (Maisonpierre et al, ), and Platelet‐derived growth factor B (Carmeliet & Jain, ; Scotti et al, ). Together, these pro‐angiogenic factors recruit peri‐vascular cells that mature and stabilize newly formed capillaries (Maisonpierre et al, ; Suri et al, ).…”

Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome

“…The alterations first described in women with PCOS were the increased VEGF concentration and ovarian blood flow (Aleem and Predanic, 1996;Battaglia et al, 1995;Kamat et al, 1995;Zaidi et al, 1995). Besides other angiogenic-related alterations in women with PCOS ovaries (Scotti et al, 2014;Tal et al, 2013aTal et al, , 2013bTal et al, , 2014Xu et al, 2011); (Artini et al, 2006;Hammadeh et al, 2003), we have previously shown that the concentration of ovarian PDGFB and PDGFD is decreased in the DHEA-induced PCOS rat model and in follicular fluid from PCOS patients (Scotti et al, 2014).…”

“…In particular, we and others have previously demonstrated that women with PCOS have higher follicular fluid concentrations of VEGF and ANGPT1 (Kamat et al, 1995;Scotti et al, 2014;Stanek et al, 2007) and an increase in ovarian stromal blood flow (Aleem and Predanic, 1996;Battaglia et al, 1995;Zaidi et al, 1995). We have recently described that PDGFB and PDGFD concentration in follicular fluid from PCOS patients are decreased compared to those of control patients (Scotti et al, 2014).…”

“…Nevertheless, we have demonstrated that the DHEA-induced PCOS rat model presents, not only the main ovarian features of human PCOS such as anovulation, absence of cyclicity, and alterations in steroidogenesis, but also increased serum insulin concentration . Interestingly, the ovaries of these rats have the same alterations in angiogenic factor concentration as PCOS women, such as increased VEGF and ANGPT1, and decreased PDGFB and PDGFD (Abramovich et al, 2012;Di Pietro et al, 2015;Scotti et al, 2014). Therefore, in the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model.…”

Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level

“…The PDGF family members include PDGF-A, PDGF-B, PDGF-C, and PDGF-D. Kalu et al detected level of factors including IL-6, TNF-ɑ and PDGF in serum from infertile women and women without endometritis [31]. Scotti et al found that PDGF-BB and PDGF-DD were significantly decreased in the follicular fluid of PCOS patients [32]. However, no report has examined the changes of PDGF-D in serum of PCOS patients.…”