INRS-Institut Armand-Frappier, 531 blvd des Prairies, Laval, QC, H7V 1B7, Canada; BioMed Research Centre, Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada; Center for Interdisciplinary Research on Well-Being, Health, Society and Environment, Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada.
BioMed Research Centre, Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada; Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada.
Toxicol Appl Pharmacol. 2018 Jun 15;349:8-20. doi: 10.1016/j.taap.2018.04.018. Epub 2018 Apr 19.
Selective serotonin-reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants during pregnancy. The human placenta is a highly specialized organ supporting normal growth and development of the fetus. Therefore, this study aims to analyze the effects of SSRIs on villous cytotrophoblasts cells, using BeWo cells and human placental trophoblast cells in primary culture. The SSRIs fluoxetine and its metabolite norfluoxetine, sertraline and venlafaxine did not affect BeWo cell proliferation and viability, nor the percentage of M30-positive (apoptotic) primary trophoblast cells. None of the SSRIs affected basal or forskolin-stimulated BeWo cell fusion, whereas sertraline and venlafaxine increased the fusion of primary villous trophoblasts. Sertraline and venlafaxine also modified human chorionic gonadotropin beta (β-hCG) secretion by BeWo cells, whereas none of the SSRIs affected β-hCG secretion in primary trophoblasts. Norfluoxetine increased CGB (chorionic gonadotropin beta) and GJA1 (gap junction protein alpha 1) levels of gene expression (biomarkers of syncytialization) in BeWo cells, whereas in primary trophoblasts none of the SSRIs tested affected the expression of these genes. This study shows that SSRIs affect villous trophoblast syncytialization in a structure- and concentration-dependent manner and suggests that certain SSRIs may compromise placental health. In addition, it highlights the importance of using primary trophoblast cells instead of "trophoblast -like" cell lines to assess the effects of medications on human villous trophoblast function.
选择性 5-羟色胺再摄取抑制剂（SSRIs）是妊娠期最常开的抗抑郁药。胎盘是人高度特化的器官，支持胎儿的正常生长发育。因此，本研究旨在分析 SSRIs 对绒毛滋养细胞的影响，使用 BeWo 细胞和原代培养的人胎盘滋养细胞。SSRIs 氟西汀及其代谢产物去甲氟西汀、舍曲林和文拉法辛均不影响 BeWo 细胞的增殖和活力，也不影响 M30 阳性（凋亡）原代滋养细胞的比例。SSRIs 均不影响基础或福司可林刺激的 BeWo 细胞融合，而舍曲林和文拉法辛增加了原代绒毛滋养细胞的融合。舍曲林和文拉法辛还改变了 BeWo 细胞分泌人绒毛膜促性腺激素β（β-hCG），而 SSRIs 均不影响原代滋养细胞中β-hCG 的分泌。去甲氟西汀增加了 BeWo 细胞中 CGB（绒毛膜促性腺激素β）和 GJA1（缝隙连接蛋白α 1）基因表达水平（合胞体化的生物标志物），而在原代滋养细胞中，没有一种 SSRIs 影响这些基因的表达。本研究表明，SSRIs 以结构和浓度依赖的方式影响绒毛滋养细胞的合胞化，并表明某些 SSRIs 可能损害胎盘健康。此外，它强调了使用原代滋养细胞而不是“滋养细胞样”细胞系来评估药物对人绒毛滋养细胞功能的影响的重要性。
