Abstract
With establishment of uteroplacental blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress that is produced by hemodynamic forces across different trophoblast subtypes. Amongst many other cell types, trophoblasts are able to sense fluid shear stress through mechanotransduction. Failure in the adaption of trophoblasts to fluid shear stress is suggested to contribute to pregnancy disorders. Thus, in the past twenty years, a significant body of work has been devoted to human- and animal-derived trophoblast culture under microfluidic conditions, using a rather broad range of different fluid shear stress values as well as various different flow systems, ranging from commercially 2D to customized 3D flow culture systems. The great variations in the experimental setup reflect the general heterogeneity in blood flow through different segments of the uteroplacental circulation. While fluid shear stress is moderate in invaded uterine spiral arteries, it drastically declines after entrance of the maternal blood into the wide cavity of the intervillous space. Here, we provide an overview of the increasing body of evidence that substantiates an important influence of maternal blood flow on several aspects of trophoblast physiology, including cellular turnover and differentiation, trophoblast metabolism, as well as endocrine activity, and motility. Future trends in trophoblast flow culture will incorporate the physiological low oxygen conditions in human placental tissue and pulsatile blood flow in the experimental setup. Investigation of trophoblast mechanotransduction and development of mechanosome modulators will be another intriguing future direction.
Highlights
With establishment of uteroplacental blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress that is produced by hemodynamic forces across different trophoblast subtypes
Establishment of maternal blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress, which is produced by plasma and hemodynamic forces across uteroplacental endothelial cells and trophoblast subtypes throughout gestation
In addition to endothelial cells, mechanosensing has recently been reported for many other cell types, including trophoblast subtypes that are exposed to fluidic flow
Summary
Human gestation involves so-called hemochorial placentation, which means that maternal blood is in direct contact with the fetal part of the placenta—the chorion frondosum, consisting of placental chorionic villi. Establishment of maternal blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress, which is produced by plasma and hemodynamic forces across uteroplacental endothelial cells and trophoblast subtypes throughout gestation. Human villous trophoblasts (HVTs), rabbit trophoblastic stem cells (rTSCs), human umbilical vein endothelial cells (HUVECs), human brain microvascular endothelial cells (HBMECs), human primary placental villous endothelial cells (HPVECs), * circulating flow loop; ** one-time inlet-to-outlet flow system; *** rotating wall vessel (RWV) bioreactor Study questions, such as to how fluidic flow and shear stress influences different aspects of trophoblast physiology (e.g., differentiation and fusion (Table 2) and migration (Table 1)), should be addressed with a most appropriate setting of the flow system. Subsequent transcriptome analysis of the rabbit trophoblasts, showed enrichment in pathways regulating actin cytoskeleton and sphingolipid metabolism, which has been suggested to account for the increased formation of microvilli during differentiation [17]
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