Effects of valproic acid on the placental barrier in the pregnant mouse: Optical imaging and transporter expression studies

Summary Our aim was to evaluate the effects of valproic acid ( VPA ) on the function of the placental barrier in vivo, in pregnant mice. Studies were conducted on gestational days 12.5 (mid‐gestation) or 17.5 (late gestation), following intraperitoneal treatment with 200 mg/kg VPA or the vehicle. Indocyanine green ( ICG ; 0.167 mg, i.v.) was used as a marker for the placental barrier permeability. Transporter expression was evaluated by quantitative ‐ PCR . VPA treatment was associated with a 40% increase (p < 0.05) in accumulation of ICG in maternal liver in mid‐pregnancy and a decrease by one fifth (p < 0.05) in late pregnancy. Ex vivo, VPA treatment led to a 20% increase (p < 0.05) in fetal ICG emission in mid‐pregnancy. Also in mid‐pregnancy, the placental expression of the L ‐type amino acid transporter, the organic anion–transporting polypeptide (Oatp)4a1 (thyroid hormone transporter), and the reduced folate carrier was lower in VPA ‐treated mice (p < 0.05). In late pregnancy, hepatic Oatp4a1 levels were 40% less than in controls (p > 0.05). The observed changes in placental transporter expression and function support further research into the potential role of the placenta in the adverse pregnancy outcomes of VPA . Near‐infrared imaging provides a noninvasive, nonradioactive tool for future studies on the effects of epilepsy and antiepileptic drugs on tissue transport functions.