Retraction. Prenatal PFOA exposure alters gene expression pathways in murine mammary gland.

Abstract

Perfluorooctanoic acid (PFOA) is a synthetic surfactant that was previously shown to delay mammary gland development in CD-1 mice. The objective of this study was to elucidate signaling pathways involved in this morphological effect. Timedpregnant CD-1 mice were treated with 0, 0.01, 0.1, or 1.0 mg PFOA/kg/day from gestational days (GD) 10–17 via oral gavage. Mammary glands from postnatal days (PND) 7 and 14 from control and 1.0 mg/kg PFOA treated mice were evaluated via genome-wide microarray analysis to identify PFOA-targeted candidate gene pathways. Selected genes from candidate pathways were evaluated by real-time PCR (RT-PCR) and Western blot analysis for RNA and protein expression changes, respectively, using samples from all treatment groups from PND 7, 14, and 21. Microarray analysis revealed that PFOA altered expression of genes involved in RNA post-transcriptional modification, lipid metabolism, and cholesterol biosynthesis pathways. These transcriptional changes were predicted to be regulated by peroxisome proliferator-activated receptor (Ppar) and endocrine related genes. Selected genes from candidate gene pathways Ppar, estrogen receptor alpha (Era/Esr1), and Wnt were further evaluated. Results from the RT-PCR analysis confirmed that genes in all 3 pathways were altered at varying levels in PFOA-exposed mammary glands. At PND 7, expression of PPARc and ERa protein were increased in a dose-dependent manner. At PND 21, mammary ERa protein expression was downregulated. PPARa protein levels were not affected. These results suggest that PFOA-induced mammary gland delays present on PND 21 may be modulated by changes in PPARc and endocrine-related genes.