Introduction: The placenta plays a critical role in fetal development, regulating nutrient and waste transfer. Vascular structure underpins these processes, and anomalies in feto-placental vascular development can impair fetal growth and result in IUGR. The aim of this study is to begin to dissect the relationship between placental vascular structure and function by modelling the haemodynamics in a rat model of control and IUGR feto-placental arterial networks.
Methods: Time-mated Wistar rats were administered with vehicle or 0.5 μg/ml dexamethasone acetate (dex) via drinking water from embryonic day (E) 12.5 until E21.5. At E21.5, individual feto-placental vascular trees were cleared of blood and arterial vasculature was cast with Microfil. 3D images of the casts were reconstructed from micro-CT scans (~7µm resolution). Geometries were analysed and one control and one dex vasculature were prepared for computational fluid dynamics (CFD) simulations. In our CFD model we used high-frequency Doppler ultrasound measurements of umbilical arterial velocity as input, split outlet flow based on Murray’s law and implemented the Fahræus-Lindqvist effect.
Results: Fetal and placental weights were decreased due to dex-exposure by 14 and 34% respectively (P<0.001). There were striking differences in vessel geometry between the control and dex models (Fig A). Distally, vessel diameters were generally comparable (<450 µm, Fig B). However, velocity and wall shear stress (WSS) were respectively 62% (P<0.001) and 65% (P<0.05) higher in the smaller vessels (<60 µm) of the control compared to the dex model (Fig C&D).
Conclusions: Here we show for the first time, the use of CFD in elucidating the relationship between placental vascular structure and haemodynamics and the impact on placental and fetal outcomes. Our preliminary findings suggest that compared to control, WSS was lower in the dex model. WSS is an important stimulus for angiogenesis and thus, in part, may underly the less elaborate vasculature that results from dex-exposure. The higher velocities in the control model influences pressure differentials at the capillary level, thus likely impacting oxygen transfer between maternal and fetal blood and contributing to the restricted fetal growth.