Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells

Abstract

BackgroundIn human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation.ResultsWe showed that hCG secretion was up-regulated by adiponectin treatment in both BeWo cells and human cytotrophoblasts from very early placentas (5-6 weeks). The expression of two trophoblast differentiation markers, leptin and syncytin 2, was also up-regulated by adiponectin in BeWo cells. Moreover, adiponectin treatment induced a loss of E-cadherin staining in these cells. In parallel, we demonstrated that AdipoR1 and AdipoR2 are up-regulated during forskolin induced BeWo cell differentiation, reinforcing the role of adiponectin in trophoblast syncytialization. SiRNA mediated down-regulation of AdipoR1 and AdipoR2 was used to demonstrate that adiponectin effects on differentiation were essentially mediated by these receptors. Finally, using a specific inhibitor, we demonstrated that the PKA signalling pathway could be one pathway involved in adiponectin effects on trophoblast differentiation.ConclusionAdiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation.

Phospholipid scramblase 1 (PLSCR1) in villous trophoblast of the human placenta

“…Furthermore, after fusion the syncytia adopt the morphology of the placental syncytiotrophoblast (Wice et al 1990) and also externalize phosphatidylserine (Das et al 2004). This makes them a valuable, frequently used and generally accepted in vitro model for studying villous trophoblast fusion (Benaitreau et al 2010;Dunk et al 2012;Mi et al 2000). To confirm that our findings from BeWo cell experiments could be translated to primary cells, we repeated the majority of our experiments in isolated primary trophoblast preparations from term placentas, which are also able to differentiate in culture, aggregate and form multinucleated syncytia (Kliman et al 1986;Yui et al 1994).…”

Adiponectin and leptin systems in human endometrium during window of implantation

“…Recent data suggest that adiponectin can also directly regulate reproductive and placental processes (17). We have recently shown in our laboratory that adiponectin promotes syncytialization and invasion capacities of human first-trimester cytotrophoblasts (18)(19)(20). In contrast to leptin, adiponectin knockout mice are fertile (21), but transgenic mice that display elevated circulating adiponectin are sterile (22).…”

Adiponectin Effect on Nitric Oxide Secretion by Normal and Endometriotic Human Endometrial Stromal Cells: in vitro Study

“…The role of adiponectin on inhibitory cell proliferation was confirmed in the cell culture. Adiponectin caused decrease of the viability and their numbers of endometrial carcinoma cell lines (HEC-1-A and RL95-2) (Cong et al, 2007) and primary trophoblast cells and trophoblast cell lines (JEG-3 and BEWO) in the culture (Benaitreau et al, 2010). Reduction of level adiponectin in body is an important agent in reproduction illness and infertility.…”