Maternal bacterial infections impact expression of drug transporters in human placenta

• Maternal bacterial infection impacts expression of transporters in human placenta.
• Infection imposes significant downregulation of ABCG2 and SLCO2B1 in placenta.
• ABCB1 mRNA expression correlates with expression of pro-inflammatory cytokines.
• Data indicate association between changes seen in animal models and human tissue.
• Clinical study of transporter-mediated effects on fetal drug exposure is needed.

BackgroundSeveral efflux and uptake transporters in the placenta are involved in the transmembrane transport of endogenous substrates and xenobiotics. Their expression and function may be altered in maternal complications associated with inflammation. Our objective was to examine the effect of chorioamnionitis, a bacterial intra-amniotic infection on the expression of clinically important transporters in human placenta.MethodsHuman placental samples were collected from preterm and term pregnancies diagnosed with chorioamnionitis infection and were gestational age-matched with samples from pregnancies with no obstetric complications, using predefined exclusion criteria. Transporter protein expression was quantified using Western blots while cytokine and transporter mRNA expression was measured via real-time polymerase chain reaction.ResultsmRNA levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α were markedly elevated by 2.5- to 3-fold in preterm placentas with infection, relative to preterm controls (p < 0.05). Expression of ABCG2 and SLCO2B1 was downregulated by 48 to 57% (p < 0.05) in placentas from women with infection and preterm parturition, relative to preterm healthy controls. Protein and mRNA expression changes were generally consistent. At term, ABCG2 mRNA and SLCO2B1 protein expression levels were significantly downregulated, relative to controls. Significant changes in ABCB1 and SLCO4A1 expression were not observed, however ABCB1 transcript levels strongly correlated with IL-6, IL-1β and TNF-α expression (p < 0.001), potentially suggesting involvement of cytokine-mediated regulation.ConclusionsCollectively, these data show that maternal infections impact the expression of key drug transporters in placenta, suggesting that materno-fetal drug transport may be altered by changes in placental expression of ABC and OATP transporters.