Vichier-Guerre Cecilia, Parker Margaret, Pomerantz Yael, Finnell Richard H, Cabrera Robert M
Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78712, United States.
Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78712, United States.
Toxicol Lett. 2017 Nov 5;281:20-25. doi: 10.1016/j.toxlet.2017.08.012. Epub 2017 Aug 24.
The use of antidepressants in pregnant women is rising, with rates up to 7.5% in the United States. Selective serotonin reuptake inhibitors (SSRIs) are currently the most common antidepressant prescribed to pregnant women. The teratogenic effects of SSRI exposure are debated because of discrepancies in epidemiological studies. As an alternative to epidemiological and animal studies, human embryonic stem cell research (hESC) provides a human-based experimental model to examine the risks of prenatal SSRI exposure. Neural crest stem cells (NCSCs) play an important role in craniofacial and cardiac development as precursors to craniofacial bones and heart septa. This study examines the effects of paroxetine (Paxil) and sertraline (Zoloft) exposure on proliferation, migration, and AP-2α protein expression of NCSC in vitro. hESCs were exposed to paroxetine and sertraline at three concentrations while undergoing directed differentiation into NCSCs. Our results indicate exposure to paroxetine significantly increased proliferation, migration, and AP-2α protein expression in NCSCs. Exposure to sertraline significantly decreased proliferation and significantly increased AP-2α protein expression in NCSC. This evidence suggests paroxetine and sertraline alter normal NCSC behavior and may thereby disrupt cardiac and craniofacial development.
孕妇使用抗抑郁药的比例正在上升，在美国高达7.5%。选择性5-羟色胺再摄取抑制剂（SSRIs）是目前给孕妇开的最常见的抗抑郁药。由于流行病学研究结果存在差异，SSRI暴露的致畸作用存在争议。作为流行病学和动物研究的替代方法，人类胚胎干细胞研究（hESC）提供了一个基于人体的实验模型，以研究产前暴露于SSRI的风险。神经嵴干细胞（NCSCs）作为颅面骨和心脏隔膜的前体，在颅面和心脏发育中起重要作用。本研究在体外检测了帕罗西汀（Paxil）和舍曲林（Zoloft）暴露对NCSC增殖、迁移和AP-2α蛋白表达的影响。hESCs在定向分化为NCSCs的过程中，以三种浓度暴露于帕罗西汀和舍曲林。我们的结果表明，暴露于帕罗西汀显著增加了NCSCs的增殖、迁移和AP-2α蛋白表达。暴露于舍曲林显著降低了NCSC的增殖，并显著增加了其AP-2α蛋白表达。这一证据表明，帕罗西汀和舍曲林改变了正常的NCSC行为，从而可能扰乱心脏和颅面发育。
