Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation

Abstract

BackgroundPolycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation.MethodsThis was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio.ResultsSerum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01).ConclusionsThese data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation

“…In addition to VEGF and PlGF, we assessed FF angiopoietin 1 and 2 levels. The production of angiopoietins are believed to assist in mediating the triggering of OHSS by hCG [27], and it has been demonstrated that angiopoietin 2, in the presence of VEGF, mediates vascular leakage to the third space [28]. Still, in the present study, we did not find an association between angiopoietins and OHSS.…”

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).…”

Association between VEGF gene polymorphisms (11 sites) and polycystic ovary syndrome risk

“…Among them, the highest score of association was KDR and FLT1 (score = 0.999); however, TGFB1, EGF, IGF1 and NOS3 had the lowest scores (0.993). The action of VEGF is mediated by binding to tyrosine kinase receptors, VEGFR-1 (Fms-like tyrosine kinase: FLT1) and VEGFR-2 (kinase domain-containing receptor: KDR) [43]. Pan et al demonstrated that HIF1A-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating PCOS [44].…”