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

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 PPARα 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 PPARα, PPARβ, and PPARγ 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 PPARα and PPARγ 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.

► Perfluorooctanoic acid (PFOA) exposure in utero induces neonatal mortality and growth deficits in mice.
► PFOA activates peroxisome proliferator-activated receptor-alpha (PPARα), a nuclear receptor pathway that regulates metabolism.
► Pregnant CD-1 mice were dosed with PFOA and expression of PPAR isoforms and regulated genes were profiled in prenatal and postnatal tissues.
► As early as GD14, PFOA affected expression of genes involved in lipid and glucose homeostasis and PPAR expression varied with age in all tissues.
► The metabolic disruption produced by PFOA may contribute to poor postnatal survival and persistent weight deficits in CD-1 mouse neonates.