Multi-scale modelling of shear stress on the syncytiotrophoblast: Could maternal blood flow impact placental function across gestation?

Abstract

The surface of the placenta is lined by a single multinucleated cell, the syncytiotrophoblast, which forms a functional barrier between maternal and fetal blood in pregnancy. The placenta plays a critical role in healthy fetal development and over the course of pregnancy forms a complex branching tree-like structure which bathes in maternal blood and serves a vital exchange function. It has been suggested that the structure of the placenta may evolve, in part, under the influence of the shear stress exerted by maternal blood flow over its surface, with the syncytiotrophoblast having a role in mechanosensing. However, data describing the mechano-sensitive nature of this cell, particularly in early gestation, is lacking. In this study we show that the syncytiotrophoblast expresses six proteins that have been related to shear sensing, and this expression is higher in the first trimester than at term. This suggests shear on the sycytiotrophoblast as an important factor influencing placental morphogenesis early in pregnancy. We then predict shear stress felt by the syncytiotrophoblast in first trimester and term placental tissue using a combination of porous medium modelling and explicit simulations of blood flow in realistic geometries derived from microCT imaging. Our models predict that typical shear stress on first-trimester tissue is higher than at term, supporting the feasibility of this mechanical stimulus as an important driver of healthy placental development.