EFFICIENT LEUCINE TRANSPORT ACROSS THE PLACENTAL BARRIER DEPENDS ON PHYSIOLOGICAL, OPPOSITELY DIRECTED LEUCINE GRADIENTS

Zaugg, Jonas; Ziegler, Fabian; Nuoffer, Jean-Marc; Moser-Hässig, Ruedi; Albrecht, Christiane (2019). EFFICIENT LEUCINE TRANSPORT ACROSS THE PLACENTAL BARRIER DEPENDS ON PHYSIOLOGICAL, OPPOSITELY DIRECTED LEUCINE GRADIENTS. Placenta, 83, e113-e113. Elsevier

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Objectives: We aimed to assess the concentrations and importance of
physiological amino acid (AA) gradients between the maternal and fetal
compartments to determine the transport activity of leucine using a 3D in
vitro model with trophoblast cells.
Methods: Maternal venous blood samples were prospectively collected
from 23 healthy patients prior to parturition by Caesarian section. The
corresponding fetal blood was sampled from placental arteries and veins
within 20 min after delivery. The acquisition of the full AA spectra was
carried out in serum by Biochrom 30+ aminoacid analyser. Statistical
analysis was performed using paired two-way ANOVA with Tukey’s
correction. The determined AA gradients were then applied in 3[H]-leucine
transfer experiments using BeWo cells in the Transwell® system to study
the kinetics of materno-fetal leucine exchange. The LAT1 (SLC7A5)-specific
inhibitor JPH203 (IC50 110 nM) was used to assess the role of LAT1 in
transplacental leucine transport.
Results: The comparison of AA concentrations between fetal and maternal
serum in healthy mother-baby pairs at birth revealed significant differences
for valine, lysine, tyrosine, glycine and glutamic acid. Glutamine was
the only AA with higher concentrations in maternal compared to fetal
serum. No significant differences in AA concentrations were observed
between female and male sera. 3[H]-leucine transfer across the trophoblast
monolayer towards the fetal side was significantly increased against a
gradient of 140 mM leucine (30 mM maternal vs. 170 mM fetal) and was
inhibited by 10 mM JPH203.
Conclusion: Efficient transport of leucine is depending on an oppositely
directed leucine gradient and is ensured mainly by the Na+-independent
transporter LAT1. High serum concentration of glutamine confirms its role
as co-substrate allowing tertiary-active transport of essential AA like
leucine against the materno-fetal gradient. Compromised leucine supply
to the developing fetus has been correlated with pregnancy diseases such
as pre-eclampsia, but the underlying mechanisms still have to be elucidated.

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