选择性5-羟色胺再摄取抑制剂(SSRIs),5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRIs),去甲肾上腺素能和特异性5-羟色胺能抗抑郁药(NaSSAs)广泛用于治疗抑郁症。抑郁症是孕妇最常见的精神疾病之一,SSRIs通常用于妊娠期抑郁症。胎盘调节母体和胎儿循环之间的营养物质和氧气的运输,对胎儿的生存和成长至关重要。本研究调查了抗抑郁药对人胎盘BeWo细胞的影响。暴露于舍曲林(SSRI)后,BeWo细胞活力显着降低,帕罗西汀(SSRI),氟伏沙明(SSRI),和度洛西汀(SNRI),而艾司西酞普兰(SSRI),文拉法辛(SNRI),和米氮平(NaSSA)几乎没有或没有影响。舍曲林增加了细胞外乳酸脱氢酶活性,帕罗西汀,氟伏沙明,还有度洛西汀,表明对细胞的毒性。舍曲林增加了细胞活性氧(ROS)的产生并降低了线粒体膜电位。舍曲林以时间和浓度依赖性方式降低细胞ATP含量。Caspase-3/7活性和凋亡细胞,使用磷脂酰丝氨酸特异性荧光探针ApotrackerGreen,舍曲林增加了。我们的研究结果表明抗抑郁药,比如舍曲林,帕罗西汀,氟伏沙明,还有度洛西汀,在人胎盘BeWo细胞中诱导毒性。舍曲林可诱导人胎盘细胞ROS依赖性凋亡。这些结果可用于进一步研究以确定孕妇抗抑郁药的最佳剂量。
Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs) are broadly used for the treatment of depression. Depression is one of the most common psychiatric disorders in pregnant women and SSRIs are commonly prescribed for depression during pregnancy. The placenta regulates the transport of nutrients and oxygen between the maternal and fetal circulation, and is essential for the survival and growth of the fetus. The present study investigated the effects of antidepressants on human placental BeWo cells. BeWo cell viability was significantly decreased following exposure to sertraline (SSRI), paroxetine (SSRI), fluvoxamine (SSRI), and duloxetine (SNRI), whereas escitalopram (SSRI), venlafaxine (SNRI), and mirtazapine (NaSSA) showed little or no effects. Extracellular lactate dehydrogenase activity was increased by sertraline, paroxetine, fluvoxamine, and duloxetine, indicating toxicity to the cells. Sertraline increased the production of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Sertraline decreased the cellular ATP content in a time and concentration-dependent manner. Caspase-3/7 activity and apoptotic cells, detected using the phosphatidylserine-specific fluorescent probe Apotracker Green, were increased by sertraline. Our findings suggest that antidepressants, such as sertraline, paroxetine, fluvoxamine, and duloxetine, induce toxicity in human placental BeWo cells. Sertraline may induce ROS-dependent apoptosis in human placental cells. These results are useful for further studies to determine the optimal dosage of antidepressants for pregnant women.