Effects of valproic acid on the placental barrier in the pregnant mouse: Optical imaging and transporter expression studies
Autor: | Shiran Udi, Miri Shmuel, Aniv Mann, Ameer Bishara, Sara Eyal, Michal Meir, Emma Portnoy |
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Rok vydání: | 2016 |
Předmět: |
Indocyanine Green
medicine.medical_specialty Placenta Gestational Age 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Fetus In vivo Pregnancy Internal medicine medicine Animals Valproic Acid business.industry Optical Imaging Age Factors Membrane Transport Proteins Transporter medicine.disease Endocrinology medicine.anatomical_structure Neurology chemistry Gene Expression Regulation Gestation lipids (amino acids peptides and proteins) Anticonvulsants Female Neurology (clinical) business Indocyanine green 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Epilepsia. 57(6) |
ISSN: | 1528-1167 |
Popis: | 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. |
Databáze: | OpenAIRE |
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