Abstract
Pregnancy increases the urinary excretion of chemicals in women and rodents. It is unknown whether the enhanced clearance of drugs during pregnancy involves changes in the expression of transporters that mediate chemical secretion and reabsorption. The purpose of this study was to quantify the mRNA and protein expression of efflux transporters in kidneys from virgin and pregnant mice on gestational days (GD) 7, 11, 14, 17, and postnatal days (PND) 1, 15, and 30 using qPCR, western blot, and immunofluorescence. Mdr1b mRNA as well as Mrp4 mRNA and protein levels decreased significantly by 25 to 75% throughout pregnancy and lactation. Similarly, Mrp2 and Mate1 mRNA expression were down-regulated 20 to 40% during mid- to late gestation but returned to control levels by PND15. In contrast, Mrp3 mRNA and protein increased 225% and 31%, respectively, at GD14. Coordinated down-regulation of brush border transporters Mate1, Mrp2, and Mrp4 and up-regulation of the basolateral Mrp3 transporter would reduce chemical secretion into urine.
- Received June 6, 2012.
- Accepted August 14, 2012.
- The American Society for Pharmacology and Experimental Therapeutics