Division of Biomedical Sciences, St George' s University of London, UK.
Cardiovasc Res. 2012 Jan 1;93(1):152-61. doi: 10.1093/cvr/cvr276. Epub 2011 Oct 19.
In early human pregnancy placental trophoblasts migrate along uterine spiral arteries (SAs) and remodel these vessels into wide-bore conduits in a process essential for successful pregnancy. Until 10-12 weeks gestation trophoblasts plug spiral arteries, resulting in slow, high-resistance blood flow. This work examined the consequences of these low shear stress conditions on trophoblast migration, adhesion molecule expression, and attraction to chemotactic factors.
Trophoblasts were cultured on fibronectin or human endothelial cells for 6-12 h under 0.5-6 dyne/cm(2) shear stress using the BioFlux200 system, and imaged by time-lapse microscopy. Computer-based imaging algorithms were developed to automatically quantify migration. Chemotaxis assays were run using parallel flow. Trophoblasts cultured on fibronectin or endothelial cells did not undergo directional migration in 0.5 and 2 dyne/cm(2) cultures; however, in 4 and 6 dyne/cm(2) trophoblasts migrated with the direction of flow (n= 4, P< 0.001). Shear stresses did not affect the speed of trophoblast migration, or adhesion molecule expression (E-selectin, α(4), β(1), and α(v)β(3) integrin). Trophoblasts cultured on endothelial cells migrated into media containing interleukin-8, macrophage chemoattractant protein-1, or Regulated-upon-Activation-Normal-T-cell-Expressed-and-Secreted (RANTES) (n= 5, P< 0.05).
Shear stress increases trophoblast migration in the direction of flow, challenging the idea that trophoblasts migrate down spiral arteries retrograde to flow. This suggests that low shear stresses generated by trophoblast plugging of spiral arteries in the first trimester may favour arterial remodelling by preventing the migration with flow seen at higher shear stresses, allowing trophoblasts to migrate down the arteries in response to alternate stimuli such as uterine or endothelial cell-derived chemotactic factors.
在人类妊娠早期，胎盘滋养层细胞沿着子宫螺旋动脉（SA）迁移，并将这些血管重塑为宽口径导管，这是成功妊娠所必需的。直到妊娠 10-12 周，滋养层细胞堵塞螺旋动脉，导致血流缓慢、阻力高。本研究探讨了这些低切应力条件对滋养层细胞迁移、黏附分子表达和对趋化因子吸引力的影响。
使用 BioFlux200 系统，在 0.5-6 达因/平方厘米的切应力下，将滋养层细胞在纤维连接蛋白或人内皮细胞上培养 6-12 小时，并通过延时显微镜进行成像。开发了基于计算机的成像算法来自动定量迁移。使用平行流动进行趋化性测定。在 0.5 和 2 达因/平方厘米的培养物中，滋养层细胞在纤维连接蛋白或内皮细胞上不进行定向迁移；然而，在 4 和 6 达因/平方厘米的切应力下，滋养层细胞沿流动方向迁移（n=4，P<0.001）。切应力不影响滋养层细胞迁移的速度或黏附分子的表达（E-选择素、α（4）、β（1）和α（v）β（3）整合素）。在含有白细胞介素-8、巨噬细胞趋化蛋白-1 或调节激活正常 T 细胞表达和分泌（RANTES）的培养基中培养的滋养层细胞迁移（n=5，P<0.05）。
切应力增加了滋养层细胞沿流动方向的迁移，这挑战了滋养层细胞逆行迁移到螺旋动脉的观点。这表明，妊娠早期滋养层细胞堵塞螺旋动脉产生的低切应力可能通过阻止在较高切应力下观察到的随流迁移，有利于动脉重塑，从而允许滋养层细胞在对其他刺激（如子宫或内皮细胞衍生的趋化因子）作出反应时向下迁移到动脉中。
