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Gene expression profiling in the lung and liver of PFOS-exposed mouse fetuses
Citation:
ROSEN, M. B., J. E. SCHMID, K. DAS, C. R. WOOD, R. ZEHR, AND C. LAU. Gene expression profiling in the lung and liver of PFOS-exposed mouse fetuses. Presented at Teratology Society, Monterey, CA, June 28 - July 03, 2008.
Impact/Purpose:
Presentation @ Teratology Meeting
Description:
The industrial surfactants perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants commonly found in the tissues of humans and wildlife. Both compounds are agonists of peroxisome proliferator-activated receptor α (PPARα) and exhibit hepatocarcinogenic potential in adult rodents. PFOS and PFOA are also developmental toxicants in rodents and PFOS has been shown to induce pulmonary deficits in rat offspring. Recent data indicate that PPARα signaling is required for neonatal mortality in PFOA-treated mice but not those exposed to PFOS. To examine the mechanism of action related to PFOS developmental toxicity, pregnant CD-1 mice were dosed with 0, 5, or 10 mg/kg PFOS from GD 1-17. Transcript profiling was conducted on the fetal liver and lung at term using Affymetrix 430_2 GeneChips. Results were contrasted to data derived from a previous PFOA study. PFOS-dependent changes were primarily related to activation of PPARα. No remarkable differences were found between PFOS and PFOA in either the fetal liver or lung, although the effects mediated by PFOS were generally less robust than those induced by PFOA. Altered functional groups included fatty acid metabolism in the fetal liver and lung as well as peroxisome biogenesis, cholesterol biosynthesis, and phospholipid biosynthesis in the fetal liver. Genes related to inflammation and proteasome biogenesis were more prominently changed in PFOA-exposed fetuses, which may reflect the greater ability of PFOA to activate PPARα. These data suggest similar transcriptional responses for PFOS and PFOA in the fetal liver and lung. Therefore, the PPARα-independent neonatal mortality observed for PFOS may reflect functional deficits related to the physical properties of the chemical rather than to transcript alterations. Data analysis is ongoing.