Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study

Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple studies have shown that taking SSRIs during pregnancy can lead to preterm birth and potential health concerns for the baby. Therefore, a biomimetic placental barrier model is utilized herein to assess transport profiles and phenotypic effects resulting from SSRI exposure, comparing fluoxetine and sertraline. Results show that the placental barrier quickly uptakes drug from the maternal side, but slowly releases on the fetal side. Phenotypically, there is a dose‐dependent change in cell adhesion molecule (CAM) and transforming growth factor beta (TGFβ) secretions, markers of cell adhesion and angiogenesis. Both drugs impact CAM secretions, whereas sertraline alone impacts TGFβ secretions. When evaluating cell type, it becomes clear that endothelial cells, not trophoblast, are the main cell type involved in these phenotypic changes. Overall, these findings further the understanding of SSRI transplacental transport and drug‐induced effects on the placental barrier. This study evaluates transport of selective serotonin reuptake inhibitors (SSRIs) across the placental barrier and the effect of SSRIs on placental barrier cells. An in vitro placental barrier shows transport profiles unique to each drug, while the whole barrier and cell‐specific studies reveal drug and cell‐specific responses for both trophoblast and endothelial cells.