PT-003 - EXPRESSION OF ABCB1 IS DECREASED IN PLACENTA OF WOMEN WITH AUTOIMMUNE DISEASE AND IN CYTOKINE- TREATED PLACENTAL EXPLANTS.

R. Asthana-Nijjar¹, A. Pollinzi¹, K. Mirdamadi¹, N. Karimian Pour¹, D. Lee², O. Nevo², M. Piquette-Miller¹; ¹University of Toronto, Toronto, ON, Canada, ²Sunnybrook Health Sciences Center, Toronto, ON, Canada.

Background: ABCB1 and ABCG2 are efflux drug transporters that are highly expressed in placenta and play a crucial role in limiting fetal exposure to potentially harmful exogenous substrates. However, maternal disease can cause their dysregulation. While autoimmune diseases (AD) affect women of childbearing age and often require therapeutic management, little is known about their effect on placental transporters. Therefore, our objective was to explore the impact of AD and inflammatory mediators on expression of ABCB1 and ABCG2 in human placenta.

Methods: The impact of AD was examined in placental samples collected from preterm (n=8) and term (n=15) pregnancies in women diagnosed with AD and gestational age matched samples from women without disease (controls, n=28). Effect of cytokines commonly elevated in AD were examined in vitro in first term placenta explants that were treated for 24 hours with 10 ng/mL of either tumor necrosis factor (TNF)-α, interleukin (IL)-6 or IL-8 and compared to media-treated controls (n=32). Expression was measured via qRT-PCR and immunodetection.

Results: As compared to controls, ABCB1 mRNA was significantly lower in preterm and term placenta from women with AD. A corresponding decrease in ABCB1 protein was seen in preterm AD. Significantly decreased ABCB1 mRNA was seen in explants treated with TNF-α or IL-8 but not IL-6. ABCG2 mRNA was not significantly altered in AD or by in vitro cytokine treatments.

Conclusion: Significantly decreased expression of ABCB1 suggest that its protective function in placenta may be compromised in AD. In vitro results indicate that disease-associated increases in inflammatory cytokines likely play a role. As this may increase fetal exposure to clinically important drugs, further studies are needed to establish the impact of these changes.