Author : Win Min Tun
Publisher :
ISBN 13 :
Total Pages : 223 pages
Book Rating : 4.:/5 (113 download)
Book Synopsis Shear Stress and Oxygen in Placental Vascular Development by : Win Min Tun
Download or read book Shear Stress and Oxygen in Placental Vascular Development written by Win Min Tun and published by . This book was released on 2019 with total page 223 pages. Available in PDF, EPUB and Kindle. Book excerpt: The placenta is an essential organ for a successful pregnancy as it develops to establish effective fetal and maternal blood supplies and materno-fetal gas exchange, both of which are crucial for fetal growth. Abnormal development of the structural components of the placenta are known to be associated with pregnancy complications including fetal growth restriction (FGR) and pre-eclampsia. The overall aim of this thesis is to understand how the placental structural aberrations observed in FGR pregnancies impact placental haemodynamics and materno-fetal gas exchange. In order to accomplish this aim, both in silico and in vitro experimental models are employed to analyse the interactions between placental structure and function in normal and FGR pregnancies.The thesis commences with an in silico study which aims to predict how the structure of the placenta impacts on the mechanical shear stress sensed by endothelial cells that form the walls of placental capillaries. A computational model of feto-placental circulation,with structure parameterised with previously published morphometric data from normal and FGR pregnancies, was used to predict placental microvascular blood flow and shear stress in normal and FGR placentae. The model predicts an elevated microvascular shear stress in FGR placentae in comparison to normal placentae and that the main parameters influencing the elevated shear stress in FGR placentae are placental volume, vascular density, radius and length of individual vascular branches. Shear stress cannot be directly measured in vivo, however, the anatomical model of the placenta considered here provides the first predictions of the magnitude and distribution of shear stress in normal and FGR placentae. The next step is to determine whether this mechanical stress can impact on endothelial cell behaviours. Using an in vitro shear stress experiment, the predicted placental microvascular shear stresses were applied to vascular endothelial cells. These endothelial cells migrated more slowly and more persistently when they were exposed to the shear stresses of FGR conditions, suggesting that normal function of endothelial cells is impaired in FGR placentae, compromising the process of blood vessel formation. We, therefore, propose a vicious cycle in FGR pregnancy, where the elevated shear stress resulting from abnormal vascular structure undermines blood vessel formation, aggravating pre-existing vascular structure abnormalities. The morphology based feto-placental haemodynamic model is extended in two ways. First the model is extended to provide a complete model of the entire fetal circulation. This allows prediction of scenarios relevant to fetal survival in a multi-scale approach, including the interaction between fetal blood pressures, cardiac output and the shear stress in the placental capillaries. Using data from the literature we explore the impact of placental resistance due to structural abnormalities on fetal cardiac function. Then, we take steps toward a personalised approach to modelling the feto-placental circulation by analysing the chorionic vascular network in normal and FGR placentae. We confirm that this network contributes to overall placental resistance in individuals, and quantify how the characteristics of this network impact on placental function in FGR. Finally, in order to understand how the placental villous structure affects on placental exchange function, a 3D computational model of placenta representing the whole organ has been developed. Normal and FGR villous structure were parameterised as reported in previous morphometric studies. The reduced villous density in FGR placentae negatively impacts the maternal blood flow velocity into intervillous space (IVS), resulting in impaired materno-fetal gas exchange and fetal growth.This thesis demonstrates the influence of placental villous and vascular structure on placental vascular shear stress and materno-fetal oxygen exchange, and contributes to the understanding of the pathophysiology of fetal growth in FGR pregnancies. It provides a concept that the in vivo physiological data, that are difficult to assess, could be predicted by developing a replica of biological system computationally.
