Differential serotonin uptake mechanisms at the human maternal–fetal interface

Abstract

Serotonin (5‐HT) plays an extensive role during pregnancy in regulating both the placental physiology and embryonic/fetal development. The uptake of 5‐HT into cells is central to the control of local concentrations of 5‐HT near its molecular targets. Here, we investigated the mechanisms of 5‐HT uptake into human primary placental cells and cord blood platelets, all isolated immediately after birth. Trophoblasts and cord blood platelets showed 5‐HT uptake with similar Michaelis constant (Km) values (~0.6 μM), typical of the high‐affinity serotonin transporter (SERT). The uptake of 5‐HT into trophoblasts was efficiently inhibited by various SERT‐targeting drugs. In contrast, the uptake of 5‐HT into feto‐placental endothelial cells was not inhibited by a SERT blocker and showed a Km value (~782 μM) in the low‐affinity range. Consistent with this, SERT mRNAs were abundant in term trophoblasts but sparse in feto‐placental endothelial cells, whereas the opposite was found for the low‐affinity plasma membrane monoamine transporter (PMAT) mRNAs. Organic cation transporter (OCT) 1, 2, and 3 mRNAs were absent or sparse in both cell types. In summary, the results demonstrate, for the first time, the presence of functional 5‐HT uptake systems in feto-placental endothelial cells and fetal platelets, cells that are in direct contact with fetal blood plasma. The data also highlight the sensitivity to various psychotropic drugs of 5‐HT transport into trophoblasts facing the maternal blood. The multiple, high‐, and low‐affinity systems present for the cellular uptake of 5‐HT underscore the importance of 5‐HT homeostasis at the maternal–fetal interface.