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.
Reprod Biol Endocrinol. 2010 Oct 29;8:128. doi: 10.1186/1477-7827-8-128.
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.
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.
Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation.
在人类妊娠中，正确的胎盘形成依赖于滋养细胞的增殖、分化、迁移和侵袭。这些过程受到胎盘激素、生长因子和细胞因子的高度调节。最近，我们已经表明，脂联素作为一种脂肪因子，对滋养细胞具有抗增殖作用。在这里，我们通过证明脂联素调节 BeWo 和人绒毛滋养细胞的分化来完成这项研究。
我们表明，脂联素处理可上调 BeWo 细胞和来自早期胎盘（5-6 周）的人绒毛滋养细胞的 hCG 分泌。脂联素还上调了 BeWo 细胞中两种滋养细胞分化标志物瘦素和合胞素 2 的表达。此外，脂联素处理诱导这些细胞中 E-钙粘蛋白染色的丧失。同时，我们证明在 forskolin 诱导的 BeWo 细胞分化过程中，AdipoR1 和 AdipoR2 上调，这加强了脂联素在滋养细胞融合中的作用。使用 siRNA 介导的 AdipoR1 和 AdipoR2 下调来证明脂联素对分化的影响主要是通过这些受体介导的。最后，使用特异性抑制剂，我们证明 PKA 信号通路可能是脂联素对滋养细胞分化影响的途径之一。
脂联素增强了滋养细胞的分化过程，因此可能参与功能性合胞体滋养层的形成。
