Phenytoin but not valproate directly affected in vitro trophoblast differentiation

Eur J Obstet Gynecol Reprod Biol. 2008 Mar;137(1):31-6. doi: 10.1016/j.ejogrb.2007.04.009. Epub 2007 May 31.

Abstract

Objective: Epilepsy has been associated with poor obstetric outcomes that could be the result of the epilepsy itself or a direct effect of anti-epileptic medication on placentation. The aim of this study was to investigate any direct effect of anti-epileptic drugs on an established, in vitro bioassay of trophoblast differentiation.

Study design: Primary extravillous trophoblast cells were cultured in the presence of phenytoin and sodium valproate at a range of concentrations with appropriate solvent controls. The formation of multinuclear giant cells was used as a marker of trophoblast differentiation.

Results: Phenytoin inhibited giant multinuclear cell formation in a dose-dependent manner; in contrast sodium valproate had no effect (p=0.011).

Conclusions: This study found that two anti-epileptic medications induced different effects on an in vitro trophoblast bioassay, suggesting that further research should be aimed at elucidating which anti-epileptic medication is most suitable for pregnant women.

MeSH terms

  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Phenytoin / pharmacology*
  • Phenytoin / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Trophoblasts / cytology*
  • Trophoblasts / drug effects
  • Valproic Acid / pharmacology*
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • Valproic Acid
  • Phenytoin