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Effect of selective serotonin reuptake inhibitors on the serotonin system and junctional protein in human placenta

Ok, Linda, Hudon-Thibeault, Andrée-Anne et Vaillancourt, Cathy ORCID: https://orcid.org/0000-0003-0543-6244 (2019). Effect of selective serotonin reuptake inhibitors on the serotonin system and junctional protein in human placenta In: 55th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology - Science Providing Solutions, 08-11 September 2019, Helsinki, Finland.

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Résumé

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most common pharmacological intervention for the treatment of antenatal depression. This type of antidepressant works by increasing the level of serotonin at the synaptic space by blocking the serotonin transporter (SERT; SLC6A4) on the post-synaptic neurons. The serotonin system, including SERT and monoamine oxidase A (MAOA), is expressed and functional in the placenta. Our group has shown that the exposure of human placenta to certain SSRIs affects the serotonin system and the trophoblast cell fusion and invasion. We hypothesized that the exposure of primary placental cells to the SSRIs alter the expression of genes involved in placental serotonergic system and the junctional proteins associated with trophoblast cells fusion. Thus, this study aims to assess the effects of most commonly used SSRIs in human trophoblasts. Primary villous trophoblasts were isolated from normal full-term human placentas and were exposed at two concentrations (0.3uM and 0.03uM) of fluoxetine, norfluoxetine, sertraline, venlafaxine, or citalopram for 24-h. The mRNA level of SLC6A4, MAOA, Connexin 43(GJA1), Tight junction protein-1(TJP-1) and Syncytin-1 (ERVW-1) were analysed by RT-qPCR. Overall, our preliminary data shows that all SSRIs tested tend to decrease the mRNA level of SLC6A4, MAOA, Connexin 43 and Zo-1 in primary trophoblasts, and were greater in the cells treated with the lower concentration (0.03uM) of Citalopram, Fluoxetine and Sertraline than the cells treated at the higher concentration (0.3uM). This preliminary study suggest that SSRI alters the mRNA expression of serotonin system and junctional proteins in human primary trophoblasts. This results need to be confirmed by further assessing the effect of SSRIs on proteins expression and placental function. The use of SSRIs during pregnancy poses adverse effect on the fetal development and may be associated with the pregnancy complications such as gestational hypertension. Thus pursuing the work is important to better understand the effect of SSRI on the placenta which is crucial for the maintenance of normal pregnancy and a healthy fetal development.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Toxicology Letters 314 (suppl.1) S274 P18-023 affiche scientifique P18-023
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 20 juill. 2021 21:32
Dernière modification: 16 févr. 2022 15:34
URI: https://espace.inrs.ca/id/eprint/11731

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