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Effects of gestational exposure to PFOA on PPAR protein and mRNA expression in vital organs of fetal and postnatal mice
Citation:
WATKINS, A., C. R. WOOD, K. DAS, C. LAU, AND B. D. ABBOTT. Effects of gestational exposure to PFOA on PPAR protein and mRNA expression in vital organs of fetal and postnatal mice. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
This study examines the expression of PPARa, B, and y in fetal and postnatal mice.
Description:
Perfluorooctanoic acid (PFOA) is developmentally toxic, causing in utero and neonatal mortality, and altering development and growth in mice. PFOA activates peroxisome proliferator-activated receptor (PPAR)a and PPARa signaling is required for toxicity. This study examines the expression of PPARa, B, and y in fetal and postnatal mice. Timed pregnant CD-1 mice were dosed orally from gestational day (GD) 1-17 with vehicle or 5 mg PFOA/kg. Tissues were collected on GD14, GD17, postnatal day (PND) 1,7, 14,21, and 28, and divided for preparation of RNA and protein. qPCR and Western blot data were normalized to internal controls (GAPDH, B-actin). PFOA exposure altered PPAR expression in liver, decreasing expression of mRNA and protein for PPARa and B on PND14. Other changes in liver included decreased mRNA for PPARa, B, and y on PND1, decreased PPARB mRNA on PND1-21, and increased PPARa mRNA on PND21 and PPARy mRNA on PND21-28. In the heart, PFOA exposure decreased PPARa mRNA on PND14 and protein on PND21. Heart PPARB mRNA decreased on PND14 and 28, and PPARy mRNA increased on PND1. In PFOA exposed kidney, PPARy mRNA was increased on PND14 and PPARB protein decreased on PND28. In the stomach, PFOA exposure decreased PPARy mRNA and protein on PND14 and mRNA remained depressed on PND21. PFOA increased PPARB protein levels in stomach on PND21. In the intestine, PFOA increased PPARy rnRNA on PND1 and 14, while PPARB mRNA was reduced on PND21. In spleen, thymus, and lung, PFOA increased PPARa mRNA on PND1 and PPARB mRNA was also increased on PND1 in spleen and thymus. PFOA decreased adrenal expression of PPARy mRNA on PND14. In addition, PPAR-, CAR-, and PXR-regulated genes were examined and effects of PFOA on expression differed between tissues. The profiles of PPAR expression and the responses to PFOA are complex. These results will be valuable for the further elucidation of PFOA's mode of action for developmental toxicity. [This abstract does not necessarily reflect US EPA policy.]