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Abstract：
The syncytiotrophoblast is a multinucleated structure that arises from fusion of mononucleated cytotrophoblasts, to sheath the placental villi and regulate transport across the maternal-fetal interface. Here, we ask whether the dynamic mechanical forces that must arise during villous development might influence fusion, and explore this question using in vitro choriocarcinoma trophoblast models. We demonstrate that mechanical stress patterns arise around sites of localized fusion in cell monolayers, in patterns that match computational predictions of villous morphogenesis. We then externally apply these mechanical stress patterns to cell monolayers and demonstrate that equibiaxial compressive stresses (but not uniaxial or equibiaxial tensile stresses) enhance expression of the syndecan-1 and loss of E-cadherin as markers of fusion. These findings suggest that the mechanical stresses that contribute towards sculpting the placental villi may also impact fusion in the developing tissue. We then extend this concept towards 3D cultures and demonstrate that fusion can be enhanced by applying low isometric compressive stresses to spheroid models, even in the absence of an inducing agent. These results indicate that mechanical stimulation is a potent activator of cellular fusion, suggesting novel avenues to improve experimental reproductive modelling, placental tissue engineering, and understanding disorders of pregnancy development.
摘要：
合胞体滋养层是由单核细胞滋养层融合产生的多核结构。覆盖胎盘绒毛并调节跨母胎界面的运输。这里,我们问绒毛发育过程中必须产生的动态机械力是否会影响融合，并利用体外绒毛膜癌滋养细胞模型探讨这一问题。我们证明了机械应力模式出现在细胞单层的局部融合位点周围，符合绒毛形态发生的计算预测的模式。然后，我们将这些机械应力模式从外部施加到细胞单层，并证明等双轴压缩应力（但不是单轴或等双轴拉伸应力）增强了syndecan-1的表达和E-cadherin的损失，作为融合的标记。这些发现表明，有助于雕刻胎盘绒毛的机械应力也可能影响发育组织的融合。然后，我们将此概念扩展到3D文化，并证明可以通过对球体模型施加低等距压缩应力来增强融合。即使没有诱导剂。这些结果表明，机械刺激是细胞融合的有效激活剂，提出改进实验性生殖模型的新途径，胎盘组织工程,了解妊娠发育障碍。
