Phenylalanine transfer across the isolated perfused human placenta: an experimental and modelling investigation

Abstract

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors such as blood flow or metabolism are poorly defined. This study combines experimental and modelling approaches to understand the determinants of 14C-phenylalanine transfer across the isolated perfused human placenta. Transfer of 14C-phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14 and 18 ml/min for one hour each. At each maternal flow rate, fetal flow rates were set at 3, 6 and 9 ml/min for 20 minutes each. Appearance of 14C-phenylalanine was measured in the maternal and fetal venous exudates. Computational modelling of phenylalanine transfer was undertaken to allow comparison of the experimental data to predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of 14C-phenylalanine increased with maternal but not fetal flow. Delivery (mol/min) of 14C-phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and its net flux to the fetal circulation suggests factors other than flow or transporter-mediated uptake are important determinants of its transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and thus placental transfer.

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Identifiers

ORCID for E.M. Lofthouse: orcid.org/0000-0002-0175-5590

ORCID for B.G. Sengers: orcid.org/0000-0001-5859-6984

ORCID for R.M. Lewis: orcid.org/0000-0003-4044-9104

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