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Effects of Selective Serotonin-Reuptake Inhibitors (SSRIs) on Migration and Invasion of Extravillous Trophoblast-Like JEG3 Cells

Clabault, Helene; Vaillancourt, Cathy; Sanderson, J. Thomas (2016). Effects of Selective Serotonin-Reuptake Inhibitors (SSRIs) on Migration and Invasion of Extravillous Trophoblast-Like JEG3 Cells In: 63RD SRI ANNUAL SCIENTIFIC MEETING VENUE, March 16-19, 2016, Montréal (Québec).

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Résumé

INTRODUCTION: Depression during pregnancy occurs in about 20% of women, of which 13% take antidepressants. SSRIs are the most commonly prescribed antidepressants for pregnant women, although their effects on placental function have never been studied. A successful pregnancy depends on healthy placental development and function. The extravillous trophoblast cells (evTBs), which invade the uterine wall, are crucial for embryo implantation and the adaptation of maternal spiral arteries. Poor invasion/migration of evTBs can cause important pregnancy complications such as preeclampsia and possibly maternal and fetal mortality. The aim of this study was to determine whether SSRIs commonly used during pregnancy affect migratory and invasive properties of JEG3 cells, used as a model of the evTBs.

METHODS: JEG3 cells were treated with increasing concentrations (0.03-10 μM) of fluoxetine, norfluoxetine or sertraline. Cell proliferation was monitored in real-time using a cell impedance-based xCELLigence system. JEG3 cell-cycle distribution was analyzed by flow cytometry. Migration was determined using a scratch test. Activities of metalloproteinases MMP-2 and MMP-9 (markers of invasion) were determined by gelatin zymography.

RESULTS: Fluoxetine and sertraline significantly decreased JEG3 cell proliferation at 10 μM by 93% and 98%, respectively ([Figure 1]-fluoxetine), compared to control, whereas norfluoxetine had no effect. Fluoxetine decreased the number of cells in the G2-M at 1 and 10 μM, and the number of cells in G0-G1 at 10 μM. None of the SSRIs affected JEG3 migration ([Figure 2]-fluoxetine) or the activities of MMP-2 and MMP-9.

Legend: Figure 1: Effect of fluoxetine on extravillous trophoblast-like JEG3 cell proliferation determined by real-time impedance monitoring. Statistically significantly different from DMSO-treated cells. Figure 2: Effect of fluoxetine on extravillous trophoblast-like JEG3 cell migration determined by scratch test.

CONCLUSIONS: This study suggests that the SSRIs fluoxetine, norfluoxetine and sertraline do not alter extravillous trophoblast viability or migration at therapeutic levels. Our observations will be verified using primary cultures of evTBs and will include additional SSRIs.

Type de document: (NON SPÉCIFIÉ)
Mots-clés libres: Affiche: Society for Reproductive Investigation- Prioritizing Reproductive Research in Times of Limited Resources
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 29 juin 2017 05:35
Dernière modification: 05 juill. 2017 14:51
URI: http://espace.inrs.ca/id/eprint/4553

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