Objective: We studied the role of multidrug resistance proteins in regulating transplacental transmission of corticosteroids and protease inhibitors.
Study design: We performed quantitative polymerase chain reaction and FACS analyses to study MDR1 (encodes P-glycoprotein) and MRP-1 expression in extravillous (HTR-8/SVneo) and villous (BeWo) trophoblast cells treated with saquinavir, a multidrug resistance protein substrate. We measured H3-dexamethasone and H3-ritonavir transfer across confluent, syncytialized BeWo cells before and after treatment with agents that inhibit multidrug resistance proteins.
Results: Compared with baseline expression, messenger RNA and protein levels were increased significantly in trophoblast cells after treatment with saquinavir. H3-dexamethasone and H3-ritonavir levels increased in BeWo cells after treatment with anti-P-glycoprotein antibodies or cyclosporine A. Transfer of H3-labeled drugs from the apical (eg, maternal) to basolateral (eg, fetal) side of the syncytialized BeWo cell monolayer was increased significantly when cells were pretreated with anti-P-glycoprotein antibodies.
Conclusion: Multidrug resistance proteins regulate drug levels in trophoblast cells and may mediate transmission of therapeutic agents across the placenta.