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

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. (c) 2010 Elsevier Ireland Ltd. All rights reserved.