Effects of Paracetamol/acetaminophen on the Expression of Solute Carriers (slcs) in Late-Gestation Fetal Rat Brain, Choroid Plexus and the Placenta

Solute carriers (SLCs) regulate transfer of a wide range of molecules across cell membranes using facilitative or secondary active transport. In pregnancy, these transporters, expressed at the placental barrier, are important for delivery of nutrients to the fetus, whilst also limiting entry of potentially harmful substances, such as drugs. In the present study, RNA-sequencing analysis was used to investigate expression of SLCs in the fetal (embryonic day 19) rat brain, choroid plexus and placenta in untreated control animals and following maternal paracetamol treatment. In the treated group, paracetamol (15 mg/kg) was administered to dams twice daily for 5 days (from embryonic day 15 to 19). In untreated animals, overall expression of SLCs was highest in the placenta. In the paracetamol treatment group, expression of several SLCs was significantly different compared with control animals, with ion, amino acid, neurotransmitter and sugar transporters most affected. The number of SLC transcripts that changed significantly following treatment was the highest in the choroid plexus and lowest in the brain. All SLC transcripts that changed in the placenta following paracetamol treatment were downregulated. These results suggest that administration of paracetamol during pregnancy could potentially disrupt fetal nutrient homeostasis and affect brain development, resulting in major consequences for the neonate and extending into childhood. What is the central question of this study?How does maternal paracetamol treatment affect expression of solute carrier (SLC) transporters in the fetal (embryonic day 19) rat brain, choroid plexus and placenta?What is the main finding and its importance?Paracetamol administered to dams at embryonic days 15-19 resulted in changed expression of a large number of SLC transporters in the placenta and the fetal brain and choroid plexus. In the placenta, all SLC transporters that changed expression were downregulated. In the fetal brain and choroid plexus, expression of SLC transporters was both up- and downregulated. These findings might have implications for development of fetuses and offspring of mothers who have taken paracetamol during pregnancy.