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Fetal growth restriction (FGR) affects 5–10% of pregnancies, leading to clinically significant fetal morbidity and mortality. FGR placentae frequently exhibit poor vascular branching, but the mechanisms driving this are poorly understood. We hypothesize that vascular structural malformation at the organ level alters microvascular shear stress, impairing angiogenesis. A computational model of placental vasculature predicted elevated placental micro-vascular shear stress in FGR placentae (0.2 Pa in severe FGR vs 0.05 Pa in normal placentae). Endothelial cells cultured under predicted FGR shear stresses migrated significantly slower and with greater persistence than in shear stresses predicted in normal placentae. These cell behaviors suggest a dominance of vessel elongation over branching. Taken together, these results suggest (1) poor vascular development increases vessel shear stress, (2) increased shear stress induces cell behaviors that impair capillary branching angiogenesis, and (3) impaired branching angiogenesis continues to drive elevated shear stress, jeopardizing further vascular formation. Inadequate vascular branching early in gestation could kick off this cyclic loop and continue to negatively impact placental angiogenesis throughout gestation.

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Significant reductions in blood flow and umbilical diameters were reported in pregnancies affected by intrauterine growth restriction (IUGR) from placental insufficiency. However, it is not known if IUGR umbilical blood vessels experience different hemodynamic wall shear stresses (WSS) compared to normal umbilical vessels. As WSS is known to influence vasoactivity and vascular growth and remodeling, which can regulate flow rates, it is important to study this parameter. In this study, we aim to characterize umbilical vascular WSS environment in normal and IUGR pregnancies, and evaluate correlation between WSS and vascular diameter, and gestational age. Twenty-two normal and 21 IUGR pregnancies were assessed via ultrasound between the 27th and 39th gestational week. IUGR was defined as estimated fetal weight and/or abdominal circumference below the 10th centile, with no improvement during the remainder of the pregnancy. Vascular diameter was determined by 3D ultrasound scans and image segmentation. Umbilical artery (UA) WSS was computed via computational flow simulations, while umbilical vein (UV) WSS was computed via the Poiseuille equation. Univariate multiple regression analysis was used to test for the differences between normal and IUGR cohort. UV volumetric flow rate, UA and UV diameters were significantly lower in IUGR fetuses, but flow velocities and WSS trends in UA and UV were very similar between normal and IUGR groups. In both groups, UV WSS showed a significant negative correlation with diameter, but UA WSS had no correlation with diameter, suggesting a constancy of WSS environment and the existence of WSS homeostasis in UA, but not in UV. Despite having reduced flow rate and vascular sizes, IUGR UAs had hemodynamic mechanical stress environments and trends that were similar to those in normal pregnancies. This suggested that endothelial dysfunction or abnormal mechanosensing was unlikely to be the cause of small vessels in IUGR umbilical cords.

Intrauterine growth restriction (IUGR) is a pregnancy complication due to placental dysfunction that prevents the fetus from obtaining enough oxygen and nutrients, leading to serious mortality and morbidity risks. There is no treatment for IUGR despite having a prevalence of 3% in developed countries, giving rise to an urgency to improve our understanding of the disease. Applying biomechanics investigation on IUGR placental tissues can give important new insights. We performed pressure-diameter mechanical testing of placental chorionic arteries and found that in severe IUGR cases (RI > 90th centile) but not in IUGR cases (RI < 90th centile), vascular distensibility was significantly increased from normal. Constitutive modeling demonstrated that a simplified Fung-type hyperelastic model was able to describe the mechanical properties well, and histology showed that severe IUGR had the lowest collagen to elastin ratio. To demonstrate that the increased distensibility in the severe IUGR group was related to their elevated umbilical resistance and pulsatility indices, we modelled the placental circulation using a Windkessel model, and demonstrated that vascular compliance (and not just vascular resistance) directly affected blood flow pulsatility, suggesting that it is an important parameter for the disease. Our study showed that biomechanics study on placenta could extend our understanding on placenta physiology.

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Intrauterine Growth Restriction (IUGR) is a serious and prevalent pregnancy complication that is due to placental insufficiency and IUGR babies suffer significantly higher risks of mortality and morbidity. Current detection rate for IUGR is generally poor and thus an alternative diagnostic tool is needed to improve the IUGR detection. Elastography, a non-invasive method that measures the tissue stiffness, has been proposed as one such technique. However, to date, we have limited information on the mechanical properties of IUGR placenta. In this study, we investigated the mechanical properties of normal and IUGR placentae and prescribed a suitable hyperelastic model to describe their mechanical behaviors. A total of 46 normal and 43 IUGR placenta samples were investigated. Results showed that placenta samples were isotropic, but had a high spatial variability of stiffness. The samples also had significant viscoelasticity. IUGR placenta was observed to be slightly stiffer than normal placenta but the difference was significant only at compression rate of 0.25 Hz and with 20% compression depth. Three simple hyperelastic models-Yeoh, Ogden and Fung models, were found to be able to fit the experimentally measured mechanical behaviors, and Fung model performed slightly better. These results may be useful for optimizing placenta elastography for the detection of IUGR.