Modulation of endocrine and transport functions in human trophoblasts by saquinavir and nelfinavir

Eur J Obstet Gynecol Reprod Biol. 2010 Sep;152(1):55-9. doi: 10.1016/j.ejogrb.2010.05.023. Epub 2010 Jun 29.

Abstract

Objectives: The distribution of drugs to the maternal-fetal interface is influenced by the expression of various efflux transporters. Among these transporters, P-glycoprotein (P-gp) is responsible for the efflux of a great number of drugs such as protease inhibitors of the human immunodeficiency virus, thus reducing the chemical exposure of the fetus.

Study design: The effects of saquinavir and nelfinavir were evaluated on human trophoblast functions and integrity by investigating their effect on human chorionic gonadotropin (hCG) secretion and on P-gp expression and functionality.

Results: Nelfinavir significantly reduced hCG secretion by 30% after a 48-h treatment but it had no effect on syncytia formation. Saquinavir had no effect on hCG secretion but significantly increased both expression (to a 2-fold extent) and functionality (by 17.9%) of P-gp, whereas nelfinavir only increased functionality (by 23.1%) with a dissociation of P-gp from caveolin-1.

Conclusion: These results suggest that the effects of saquinavir and nelfinavir differ on trophoblast functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Caveolin 1 / metabolism
  • Chorionic Gonadotropin / metabolism
  • Female
  • Giant Cells / drug effects
  • HIV Protease Inhibitors / pharmacology*
  • Humans
  • Maternal-Fetal Relations / drug effects*
  • Nelfinavir / pharmacology*
  • Pregnancy
  • Saquinavir / pharmacology*
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Caveolin 1
  • Chorionic Gonadotropin
  • HIV Protease Inhibitors
  • Nelfinavir
  • Saquinavir