Maternal-fetal cholesterol transfer in human term pregnancies.

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.

Placental release of taurine to both the maternal and fetal circulations in human term pregnancies.

Taurine is regarded as an essential amino acid in utero, and fetal taurine supply is believed to rely solely on placental transfer from maternal plasma. Despite its potential role in intrauterine growth restriction and other developmental disturbances, human in vivo studies of taurine transfer between the maternal, placental, and fetal compartments are scarce. We studied placental transfer of taurine in uncomplicated human term pregnancies in vivo in a cross-sectional study of 179 mother-fetus pairs. During cesarean section, we obtained placental tissue and plasma from incoming and outgoing vessels on the maternal and fetal sides of the placenta. Taurine was measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences, and measured placental expression of the taurine biosynthetic enzyme cysteine sulfinic acid decarboxylase (CSAD) with quantitative real-time polymerase chain reaction and western blot. We observed a fetal uptake (p < 0.001), an uteroplacental release (p < 0.001), and a negative placental consumption of taurine (p = 0.001), demonstrating a bilateral placental release to the maternal and fetal compartments. Increasing umbilical vein concentrations and fetal uptake was associated with the uteroplacental release to the maternal circulation (rs = - 0.19, p = 0.01/rs = - 0.24, p = 0.003), but not with taurine concentrations in placental tissue. CSAD-mRNA was expressed in placental tissue, suggesting a potential for placental taurine synthesis. Our observations show that the placenta has the capacity to a bilateral taurine release, indicating a fundamental role of taurine in the human placental homeostasis beyond the supply to the fetus.

Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

OBJECTIVES: The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample. METHODS: This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations. RESULTS: In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake. CONCLUSIONS: Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the result of a dynamic interplay between fetal and placental amino acid metabolism and interconversions.