Search

Background: Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels., Objective: We describe placental growth factor, soluble Fms-like tyrosine kinase 1, soluble endoglin, and endothelin 1-3 in 5 vessels in healthy pregnancies, early- and late-onset preeclampsia. Specifically, we aimed to (1) compare protein abundance in vessels at the maternal-fetal interface between early- and late-onset preeclampsia, and healthy pregnancies, (2) describe placental uptake and release of proteins, and (3) describe protein abundance in the maternal vs fetal circulations., Study Design: Samples were collected from the maternal radial artery, uterine vein and antecubital vein, and fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs (including 19 early-onset preeclampsia and 18 late-onset preeclampsia), during scheduled cesarean delivery. This method allows estimation of placental release and uptake of proteins by calculation of venoarterial differences on each side of the placenta. The microarray-based SomaScan assay quantified the proteins., Results: The abundance of soluble Fms-like tyrosine kinase 1 and endothelin 1 was higher in the maternal vessels in preeclampsia than in healthy pregnancies, with the highest abundance in early-onset preeclampsia. Placental growth factor was lower in the maternal vessels in early-onset preeclampsia than in both healthy and late-onset preeclampsia. Maternal endothelin 2 was higher in preeclampsia, with late-onset preeclampsia having the highest abundance. Our model confirmed placental release of placental growth factor and soluble Fms-like tyrosine kinase 1 to the maternal circulation in all groups. The placenta released soluble Fms-like tyrosine kinase 1 into the fetal circulation in healthy and late-onset preeclampsia pregnancies. Fetal endothelin 1 and soluble Fms-like tyrosine kinase 1 were higher in early-onset preeclampsia, whereas soluble endoglin and endothelin 3 were lower in both preeclampsia groups than healthy controls. Across groups, abundances of placental growth factor, soluble Fms-like tyrosine kinase 1, and endothelin 3 were higher in the maternal artery than the fetal umbilical vein, whereas endothelin 2 was lower., Conclusion: An increasing abundance of maternal soluble Fms-like tyrosine kinase 1 and endothelin 1 across the groups healthy, late-onset preeclampsia and early-onset combined with a positive correlation may suggest that these proteins are associated with the pathophysiology and severity of the disease. Elevated endothelin 1 in the fetal circulation in early-onset preeclampsia represents a novel finding. The long-term effects of altered protein abundance in preeclampsia on fetal development and health remain unknown. Further investigation of these proteins' involvement in the pathophysiology and as treatment targets is warranted., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The extent to which the human term fetus utilizes cholesterol released from the placenta has remained elusive. Our aims were to estimate the net mass of cholesterol taken up by the uteroplacental unit, released by the placenta and taken up by the fetus. Thereby we aimed to explore the maternal-fetal cholesterol transfer and hypothesized that maternal levels and uteroplacental uptake were correlated to the fetal uptake of cholesterol., Methods: A cross-sectional in vivo study of 179 fasting, healthy women with uncomplicated singleton pregnancies. Blood flow in the uterine artery (n = 70) and umbilical vein (n = 125) was measured by Doppler ultrasound. Blood samples from the maternal radial artery, antecubital vein and uterine vein, and the umbilical artery and vein were obtained during cesarean section. Cholesterol was determined enzymatically., Results: We found a significant uteroplacental uptake (median [Q1,Q3]) of total (3.50 [-36.8,61.1]) and HDL cholesterol (6.69 [-3.78,17.9]) μmol/min, and a fetal uptake of HDL (8.07 [4.48,12.59]), LDL (5.97 [2.77,8.92]) and total cholesterol (13.2 [8.06,21.58]) μmol/min. Maternal cholesterol levels were not correlated to fetal uptake of cholesterol. There was a correlation between uteroplacental uptake of total (rho 0.35, p 0.003) and LDL cholesterol (rho 0.25, p 0.03) and the fetal uptake of LDL cholesterol from the umbilical circulation. The fetal uptake of cholesterol from HDL was higher than from LDL (p < 0.001)., Conclusion: Fetal cholesterol uptake is independent of maternal cholesterol levels, but related to the uteroplacental uptake of cholesterol from LDL. This suggests that the placenta influences maternal-fetal cholesterol transfer at term., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Vast amounts of data show associations between maternal obesity, dysglycemia, diabetes, and undernutrition during pregnancy and increased cardiovascular disease risk in offspring. However, elevated maternal LDL cholesterol (LDL-C) in pregnancy and offspring cardiovascular disease (CVD) risk has scarcely been studied., Objective: Our objective was to investigate the associations between elevated maternal LDL-C in pregnancy and CVD risk factors in 6-to-13-year-old offspring., Methods: We recruited 6-to-13-year-old children whose mothers attended a pregnancy cohort and who had high or low cholesterol in pregnancy, defined as LDL-C over the 90th percentile or below the 10th percentile within the pregnancy cohort, respectively. We measured CVD risk factors in the children in the 2 groups., Results: Maternal plasma LDL-C at gestational week 14 to 16 was 4.0 and 1.4 mmol/L in the hypercholesterolemic (n = 27) and hypocholesterolemic (n = 34) groups, respectively (P < .001). Interestingly, offspring plasma LDL-C was 0.4 mmol/L higher in children whose mothers had hypercholesterolemia during pregnancy (P < .01). We found no difference in birthweight or any other clinical or biochemical CVD risk factors or dietary intake between the children at 6-13 years., Conclusions: Women with elevated LDL-C during early pregnancy have offspring with higher LDL-C already at the age of 6-13 years. Unless cholesterol-reducing measures are successfully implemented, the affected children may be at increased cardiovascular risk., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)