Differential serotonin uptake mechanisms at the human maternal-fetal interface

Bakovic, P.; Kesic, M.; Horvaticek, M.; George, M.; Peric, M.; Cicin-Sain, L.; Desoye, G.; Wadsack, C.; Panzenboeck, U.; Stefulj, J.

doi:10.1101/2021.01.07.425725

bioRxiv · 10.1101/2021.01.07.425725

Differential serotonin uptake mechanisms at the human maternal-fetal interface

Bakovic, P.·Kesic, M.·Horvaticek, M.·George, M.·Peric, M.·Cicin-Sain, L.·Desoye, G.·Wadsack, C.·Panzenboeck, U.·Stefulj, J.

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Abstract

Mechanisms regulating serotonin (5-HT) homeostasis at the maternal-fetal interface are important for proper placental functioning and fetal (neuro)development. Here we studied 5-HT uptake mechanisms in human primary trophoblasts, feto-placental endothelial cells and cord blood platelets, all isolated directly after birth. Trophoblasts and cord blood platelets demonstrated high-affinity 5-HT uptake with similar Michaelis constant (Km) values (0.60{+/-}0.27 and 0.65{+/-}0.18 M, respectively). In contrast, feto-placental endothelial cells displayed saturation kinetics only over the low-affinity range of 5-HT concentrations (Km=782{+/-}218 M). 5-HT uptake into trophoblasts was inhibited by various psychotropic drugs targeting high-affinity serotonin transporter (SERT), and into feto-placental endothelial cells by an inhibitor of low-affinity transporters. SERT mRNAs were abundant in trophoblasts, but sparse in feto-placental endothelial cells; the opposite was found for transcripts of the low-affinity plasma membrane monoamine transporter (PMAT). These results show for the first time the presence of functional 5-HT uptake systems in feto-placental endothelial cells and fetal platelets, cells in direct contact with the fetal blood plasma. Data also emphasize sensitivity of 5-HT transport into trophoblasts, cells facing maternal blood, to various psychotropic drugs. The multiple, high- and low-affinity, systems present for cellular 5-HT uptake highlight the importance of maintaining 5-HT homeostasis at the maternal-fetal interface.

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Bakovic, P., Kesic, M., Horvaticek, M., George, M., Peric, M., Cicin-Sain, L., Desoye, G., Wadsack, C., Panzenboeck, U., Stefulj, J.. 2021-01-07. Differential serotonin uptake mechanisms at the human maternal-fetal interface. https://doi.org/10.1101/2021.01.07.425725

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