Effects of paracetamol (acetaminophen) on the expression of solute carriers (SLCs) in late gestation fetal rat brain, choroid plexus and the placenta

Abstract

Abstract 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 developing 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 (E19) rat brain, choroid plexus and placenta in untreated controls and following maternal paracetamol treatment. In the treated group, paracetamol (15 mg/kg) was administered to dams twice daily for 5 days (from E15 to E19). Expression of several SLCs was significantly different in paracetamol treatment group compared to controls in all tissues tested, 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. In control tissues, overall expression of SLCs was highest in the placenta. However, following paracetamol treatment, SLC transcripts in the placenta were either unchanged or significantly lower. Together, these results suggest that administration of paracetamol during pregnancy could potentially disrupt fetal nutrient homeostasis and affect brain development.