Optimal development of placental vasculature is fundamental to placental function and fetal growth. The structure of the fetal side of the placental circulation determines both biomechanical forces (shear stress and pressure) on the endothelium, and blood flow deceleration towards the capillary level to facilitate capillary oxygenation. To better understand these relationships, we used a well-established rat model of fetal growth restriction. Pregnant Wistar rats were administered dexamethasone acetate (Dex) from embryonic day (E)13.5 until E21.5. Three-dimensional feto-placental vascular casts were obtained from control (n=8) and Dex (n=8) pregnancies. These were analysed for structural changes and the 3D geometries were used for computational fluid dynamics simulations with high-frequency Doppler ultrasound measurements implemented as input to the model. Biomechanical forces, downstream velocities and oxygenation were extracted as mean time-averaged values.
Dex reduced fetal (-21%; p<.0001) and placental (-36%; p<.0001) weights relative to controls. Placental tissue volume (-39% p<.01) and vessel volume (-53% p<.001), number (-62% p<.05) and length (-48%; p<.05) were also reduced. There were minimal differences in umbilical artery Doppler velocity, yet simulations revealed terminal velocities near the capillary bed were 57% (p<.05) greater in Dex placentas relative to controls and consequentially, overall Dex placental oxygenation was 69% (p<.05) lower. Shear stress and pressure were 46% (p<0.05) and 86% (p<0.05) higher in Dex placentas, with differences pronounced in smaller vessels.
The reduced vascular complexity of Dex placentas prevented normal blood flow deceleration, hence reducing oxygen diffusion. The observed increase in shear stress may indicate flow-mediated vasodilation occurs as a response to impaired vascular structure, but at the expense of flow deceleration. Moreover, the homeostatic response to increased pressure could cause increased arterial stiffness, previously reported in growth-restricted fetuses. Ongoing work involving fetal-placental gene expression and other gestational timepoints will provide a deeper understanding of placental function and fetal growth restriction.