Effects of perfluorooctanoic acid (PFOA) on expression of peroxisome proliferator-activated receptors (PPAR) and nuclear receptor-regulated genes in fetal and postnatal CD-1 mouse tissues
- 作者：Barbara D. Abbott ; Abbott.barbara@epa.gov ; Carmen R. Wood ; Andrew M. Watkins ; Katoria Tatum-Gibbs ; Kaberi P. Das ; Christopher Lau
- 关键词：Perfluorooctanoic acid (PFOA) ; Peroxisome proliferator activated receptor-alpha (PPAR伪) ; Peroxisome proliferator activated receptor-beta (PPAR尾) ; Peroxisome proliferator activated receptor-gamma (PPAR纬) ; Developmental toxicity
- 刊名：Reproductive Toxicology
- 出版年：2012
- 期刊代码：233_08906238
- 类别：med
- 出版时间：July, 2012
- 卷：33
- 期：4
- 页码：491-505
- 文件大小：1762 K
摘要
PPARs regulate metabolism and can be activated by environmental contaminants such as perfluorooctanoic acid (PFOA). PFOA induces neonatal mortality, developmental delay, and growth deficits in mice. Studies in genetically altered mice showed that PPAR伪 is required for PFOA-induced developmental toxicity. In this study, pregnant CD-1 mice were dosed orally from GD1 to 17 with water or 5 mg PFOA/kg to examine PPAR伪, PPAR尾, and PPAR纬 expression and profile the effects of PFOA on PPAR-regulated genes. Prenatal and postnatal liver, heart, adrenal, kidney, intestine, stomach, lung, spleen, and thymus were collected at various developmental ages. RNA and protein were examined using qPCR and Western blot analysis. PPAR expression varied with age in all tissues, and in liver PPAR伪 and PPAR纬 expression correlated with nutritional changes as the pups matured. As early as GD14, PFOA affected expression of genes involved in lipid and glucose homeostatic control. The metabolic disruption produced by PFOA may contribute to poor postnatal survival and persistent weight deficits of CD-1 mouse neonates.