The developing fetus is highly vulnerable to imbalances in the supply of essential amino acids (AA). Transplacental AA transfer depends on complex interactions between accumulative transporters, exchangers and facilitators, which maintain both intra-extracellular and materno-fetal substrate gradients. We determined physiological AA gradients between maternal and fetal blood and assessed their importance by studying maternal-fetal leucine transfer in human trophoblasts. Maternal-venous and corresponding fetal-arterial/fetal-venous sera were collected from 22 healthy patients at partum. The acquisition of the full AA spectra in serum was performed by ion exchange chromatography. Physiological materno-fetal AA levels were evaluated using paired two-way ANOVA with Tukey's correction. AA concentrations and gradients were tested for associations with anthropometric data by Spearman correlation analysis. Functional effects of a physiological leucine gradient versus equimolar concentrations were tested in BeWo cells using L-[3H]-leucine in conventional and Transwell-based uptake and transfer experiments. The LAT1/SLC7A5-specific inhibitor JPH203 was used to evaluate...

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