Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells
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RESEARCH
Open Access
Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells Delphine Benaitreau, Esther Dos Santos, Marie-Christine Leneveu, Philippe De Mazancourt, René Pecquery, Marie-Noëlle Dieudonné*
Abstract Background: In 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. Results: We 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. Conclusion: Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation.
Background In human pregnancy, trophoblast cells play an essential role in embryo implantation and placental development. These cells differentiate according to one of two distinct pathways. In the extravillous pathway, cytotrophoblasts (CT) proliferate, differentiate into an invasive phenotype, and penetrate into the maternal decidua and myometrium [1,2]. In the villous pathway, mononuclear CT fuse to form a specialized multinuclear syncytium called syncytiotrophoblast (ST) on the outer layer of placental villi [1]. ST formation plays an important role in human placentation. This process might be affected in some pathological pregnancy situations. For example, altered ST formation was observed in human preeclampsia [2]. * Correspondence: [email protected] Université de Versailles-St Quentin, Service de Biochimie et Biologie Moléculaire, UPRES-EA 2493, Faculté de Médecine Paris-Ile de France Ouest, PRES Universud Paris, Centre Hospitalier de Poissy-Saint Germain, 78303 Poissy Cedex, France
The ST layer is the site of many placental functions necessary for foetal growth and development, including nutrient, gas exchanges, and synthesis of steroid and peptide hormones [2]. Characteristics related to trophoblast differentiation include the production of hormones lik
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