Impact of selective serotonin reuptake inhibitors on neural crest stem cell formation

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.

Keywords: Human embryonic stem cells; In vitro toxicity testing; Neural crest stem cells; Paroxetine; Paxil; Selective serotonin reuptake inhibitors; Sertraline; Zoloft.

MeSH terms

  • Antidepressive Agents / toxicity*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects*
  • Gene Expression Regulation
  • Humans
  • Neural Crest / cytology
  • Neural Crest / drug effects*
  • Paroxetine / toxicity
  • Serotonin Uptake Inhibitors / toxicity*
  • Sertraline / toxicity
  • Transcription Factor AP-2 / genetics
  • Transcription Factor AP-2 / metabolism


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Transcription Factor AP-2
  • Paroxetine
  • Sertraline