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

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.

Keywords: P-glycoprotein, Trophoblast cells, Placenta, hCG, Saquinavir, Nelfinavir, Caveolin-1