3D visualization of trans-syncytial nanopores provides a pathway for paracellular diffusion across the human placental syncytiotrophoblast.
3D visualization of trans-syncytial nanopores provides a pathway for paracellular diffusion across the human placental syncytiotrophoblast.
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DOI：
10.1016/j.isci.2022.105453
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发表时间：
2022-12-22
期刊：
影响因子：
5.8
通讯作者：
Sengers, Bram G.
中科院分区：
文献类型：
--
作者：
Lewis, Rohan M.;Baskaran, Harikesan;Green, Jools;Tashev, Stanimir;Palaiologou, Eleni;Lofthouse, Emma M.;Cleal, Jane K.;Page, Anton;Chatelet, David S.;Goggin, Patricia;Sengers, Bram G.
胎盘合体滋养层是一种没有细胞与细胞连接的合体，是母亲和胎儿之间的主要屏障。尽管在合体滋养层中溶质的旁细胞扩散没有明显的解剖学途径，但观察到大小依赖性的旁细胞扩散。在这里，我们报告的数据表明，合体滋养层被跨合体纳米孔（TSN）打断。这些膜结合的 TSN 直接连接合体滋养层面向母体和胎儿的侧面，为母体和胎儿之间的细胞旁扩散提供了途径。基于 TSN 3D 几何形状的 TSN 渗透性数学模型表明，每 cm3 胎盘组织有 10-3700 万个 TSN 可以解释实验观察到的胎盘细胞旁扩散。 TSN 可以介导母体和胎儿循环之间的生理静水压和渗透压稳态，但也会使胎儿暴露于药物、环境污染物和纳米颗粒。胎盘合体滋养层被跨合体纳米孔打断 跨合体纳米孔提供了细胞旁扩散的途径 3D 纳米孔结构的计算模型可以估计其渗透性 跨合体纳米孔可能介导胎儿接触亲水性药物和毒素数学生物科学；生物科学研究方法论
The placental syncytiotrophoblast, a syncytium without cell-cell junctions, is the primary barrier between the mother and the fetus. Despite no apparent anatomical pathway for paracellular diffusion of solutes across the syncytiotrophoblast, size-dependent paracellular diffusion is observed. Here we report data demonstrating that the syncytiotrophoblast is punctuated by trans-syncytial nanopores (TSNs). These membrane-bound TSNs directly connect the maternal and fetal facing sides of the syncytiotrophoblast, providing a pathway for paracellular diffusion between the mother and fetus. Mathematical modeling of TSN permeability based on their 3D geometry suggests that 10–37 million TSNs per cm3 of placental tissue could explain experimentally observed placental paracellular diffusion. TSNs may mediate physiological hydrostatic and osmotic pressure homeostasis between the maternal and fetal circulations but also expose the fetus to pharmaceuticals, environmental pollutants, and nanoparticles. The placental syncytiotrophoblast is punctuated by trans-syncytial nanopores Trans-syncytial nanopores provide a route for paracellular diffusion Computational modeling of 3D nanopore structure allowed estimation of their permeability Trans-syncytial nanopores may mediate fetal exposure to hydrophilic drugs and toxins Physiology; Mathematical biosciences; Biological sciences research methodologies
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