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GENE PROFILING IN THE LUNG AND LIVER OF PFOA EXPOSED MOUSE FETUSES
Citation:
ROSEN, M. B., J. R. THIBODEAUX, C. R. WOOD, R. ZEHR, J. E. SCHMID, AND C. S. LAU. GENE PROFILING IN THE LUNG AND LIVER OF PFOA EXPOSED MOUSE FETUSES. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Perfluorooctanoic acid (PFOA) is a stable perfluoroalkyl acid (PFAA) used to synthesize fluoropolymers during the manufacture of a wide variety of products. Concerns have been raised over the potential health effects of PFAAs, in part, due to the persistence of these fluorinated organic molecules in the environment. In particular, PFOA and perfluorooctane sulfonate (PFOS) have been of interest because they can be detected at low concentrations in the blood and other tissues of many animal species, including humans, and have demonstrated toxicity in laboratory animals. Both compounds, for example, have been shown to induce growth deficits and mortality in rodent neonates. To better understand the mechanism of PFOA induced developmental toxicity we have initiated studies to examine the lung and liver gene expression profiles from exposed full-term mouse fetuses. In the current experiment, 15 timed-pregnant CD-1 mice were orally dosed from GD 2-19 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 per treatment group were then evaluated using Affymetrix mouse 430_2 microarrays. Pronounced changes in gene expression, especially in the fetal liver, were observed at either dose. Upregulation of genes involved in fatty acid metabolism, oxidative phosphorylation and glutathione metabolism were evident in the fetal liver while similar changes in fatty acid metabolism were also observed in the fetal lung. These alterations are consistent with activation of PPAR signaling. Along those lines, notable downregulation of Serpin1a was observed across both tissues as was upregulation of FABP-1, Cyp4a14, Cyp4a10, and Aldh1a7. Modest changes in the expression of Beta-catenin, Nfib, and Foxf1a in the lung also suggested possible effects of PFOA on lung maturation. This abstract does not necessarily reflect EPA policy.