Effects of selective serotonin-reuptake inhibitors (SSRIs) on human villous trophoblasts syncytialization

Clabault, Hélène; Flipo, Denis; Gadrey, Jean; Fournier, Thierry; Sanderson, J. Thomas; Vaillancourt, Cathy

doi:10.1016/j.taap.2018.04.018

Cited by 25 publications

(24 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When evaluating the whole model, it was observed that sertraline, not fluoxetine, significantly reduced TGFβ expression, suggesting some level of distinct drug effects. This supports the hypothesis that there are drug‐specific effects, where each SSRI elicits a unique change in cell physiology, which has been previously shown for placental cells . For example, Clabault et al showed that sertraline, but not fluoxetine or its metabolite norfluoxetine, increased syncytialization of primary trophoblast (i.e., fusion of cells toward the syncytiotrophoblast) and reduced human chorionic gonadotropin (hCG) secretions, a key pregnancy hormone, in BeWo cells .…”

Section: Discussionsupporting

confidence: 76%

“…This supports the hypothesis that there are drug‐specific effects, where each SSRI elicits a unique change in cell physiology, which has been previously shown for placental cells . For example, Clabault et al showed that sertraline, but not fluoxetine or its metabolite norfluoxetine, increased syncytialization of primary trophoblast (i.e., fusion of cells toward the syncytiotrophoblast) and reduced human chorionic gonadotropin (hCG) secretions, a key pregnancy hormone, in BeWo cells . Similarly, Kapoor et al observed that sertraline, not fluoxetine, impacts P‐gp function in brain ECs .…”

Section: Discussionsupporting

confidence: 73%

“…By comparison, trophoblast CAM secretions were almost an order of magnitude lower than the ECs, suggesting that SSRIs have a minimal, if any, impact on these secretions. Moreover, to the authors' knowledge, SSRI‐induced changes to trophoblast secretions were not previously studied, although Clabault et al found that SSRIs, particularly sertraline, appear to impact trophoblast syncytialization in a dose‐dependent manner, suggesting that SSRIs may impact the trophoblast layer and its barrier properties, though likely not through CAMs. Similar to the study by Clabault et al, sertraline seemed to elicit a more dramatic response than fluoxetine, further suggesting that sertraline may be more detrimental to the BPB than fluoxetine.…”

Section: Discussionmentioning

confidence: 93%

“…Additionally, trophoblast cell lines were utilized in coculture with primary umbilical vein ECs. As other studies have shown, there are differences based upon the trophoblast cell line used or if primary trophoblast are used, and thus some of the effects may not be observed when using cell lines . Additional further studies utilizing primary trophoblast would help to alleviate these concerns and elucidate the observed effects.…”

Section: Discussionmentioning

confidence: 98%

“…Studies evaluating using these drugs during pregnancy did not occur until nearly a decade after the drugs were approved, with studies focusing on neonatal outcomes . Since then, studies have shown SSRIs induce the intended neurological effects, but also side effects on other tissues, including neurodevelopmental effects, cardiovascular‐related effects, effects on endothelial cells (ECs), and effects on the placenta itself and downstream fetal tissue . As it is widely accepted that SSRIs readily pass through the placenta and can impact fetal development, studies related to the role of the placenta and drug‐induced effects on the BPB have become increasing important .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Arumugasaamy

Gudelsky

Hurley-Novatny

et al. 2019

Adv Healthcare Materials

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Arumugasaamy

Gudelsky

Hurley-Novatny

et al. 2019

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

Pharmacokinetics and Transplacental Transfer of Fluoxetine Enantiomers and Their Metabolites in Pregnant Women

Carvalho

Lanchote

Filgueira

et al. 2018

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Considering that fluoxetine (FLX) is used to treat depressive states during pregnancy and that it is a cytochrome P450 (CYP)2D6 inhibitor, which is involved in the metabolism of both of its enantiomers, this study aims to describe the enantioselective distribution and metabolism of FLX and of its metabolite norfluoxetine (NorFLX) following a single oral dose. Nine healthy pregnant women received 20 mg FLX at 32 weeks of gestation and later at the day of delivery. The apparent clearance of (S)-(+)-FLX (1.45 vs. 0.66 L/hour/kg) and the area under the plasma concentration vs. time curve (AUC) of the (S)-(+)-NorFLX (AUC 0-∞ 942.7 vs. 498.6 ng hour/mL) were higher (P < 0.05) than those of the respective (R)-(−) enantiomers, indicating that the (S)-(+)-FLX enantiomer is preferentially metabolized to (S)-(+)-NorFLX. The placental transfer (umbilical vein/maternal vein) of FLX and NorFLX is low (30-40%), with the predominant transfer of (S)-(+)-FLX (44 vs. 33%). The distribution of the enantiomers of FLX and NorFLX to amniotic fluid is low (< 10%).

show abstract

The placenta‐brain‐axis

Rosenfeld

2020

J of Neuroscience Research

156

View full text Add to dashboard Cite

All mammalian species depend on the placenta, a transient organ, for exchange of gases, nutrients, and waste between the mother and conceptus. Besides serving as a conduit for such exchanges, the placenta produces hormones and other factors that influence maternal physiology and fetal development. To meet all of these adaptations, the placenta has evolved to become the most structurally diverse organ within all mammalian taxa. However, commonalities exist as to how placental responses promote survival against in utero threats and can alter the trajectory of fetal development, in particular the brain. Increasing evidence suggests that reactions of the placenta to various in utero stressors may lead to long‐standing health outcomes, otherwise considered developmental origin of health and disease effects. Besides transferring nutrients and gases, the placenta produces neurotransmitters, including serotonin, dopamine, norepinephrine/epinephrine, that may circulate and influence brain development. Neurobehavioral disorders, such as autism spectrum disorders, likely trace their origins back to placental disturbances. This intimate relationship between the placenta and brain has led to coinage of the term, the placenta‐brain‐axis. This axis will be the focus herein, including how conceptus sex might influence it, and technologies employed to parse out the effects of placental‐specific transcript expression changes on later neurobehavioral disorders. Ultimately, the placenta might provide a historical record of in utero threats the fetus confronted and a roadmap to understand how placenta responses to such encounters impacts the placental‐brain‐axis. Improved early diagnostic and preventative approaches may thereby be designed to mitigate such placental disruptions.

show abstract

Effects of selective serotonin-reuptake inhibitors (SSRIs) on human villous trophoblasts syncytialization

Cited by 25 publications

References 87 publications

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

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

Pharmacokinetics and Transplacental Transfer of Fluoxetine Enantiomers and Their Metabolites in Pregnant Women

The placenta‐brain‐axis

Contact Info

Product

Resources

About