Exposure to PFOA during gestation altered the expression of genes related to fatty acid catabolism in both the fetal liver and lung. In the fetal liver, the effects of PFOA were robust and also included genes associated with lipid transport, ketogenesis, glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis, steroid metabolism, bile acid biosynthesis, phospholipid metabolism, retinol metabolism, proteosome activation, and inflammation. These changes are consistent with activation of PPAR alpha. Non-PPAR alpha related changes were suggested as well.
Keywords: gene expression, microarray,PFOA, mouse, fetus, liver
Overall design: Experiment 1: High Dose: Thirty timed-pregnant CD-1 mice were orally dosed from gestation day 1-17 with either 0, 5, or 10 mg/kg/day PFOA in water. At term, fetal lung and liver were collected, total RNA prepared, and samples pooled from three fetuses per litter. Five biological replicates consisting of individual litter samples were then evaluated for treatment group using Affymetrix mouse 430_2 microarrays.
Experiment 2: Low Dose: Thirty timed-pregnant CD-1 mice were orally dosed from gestation day 1-17 with either 0, 1, or 3 mg/kg/day PFOA in water. At term, fetal lung and liver were collected, total RNA prepared, and samples pooled from three fetuses per litter. Five biological replicates consisting of individual litter samples were then evaluated for treatment group using Affymetrix mouse 430_2 microarrays (note one microarray from the lung + 1mg/kg/day dose group was excluded from the study due to high background).
Please note that each dose experiment had separate concurrent controls.
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