Perinatal Exposure to Purity-Controlled Polychlorinated Biphenyl 52, 138, or 180 Alters Toxicogenomic Profiles in Peripheral Blood of Rats after 4 Months

Abstract

It is known from controlled animal experiments and human epidemiologic studies that early life exposure to mixtures of polychlorinated biphenyls (PCBs) is a risk factor for developmental neurotoxicity. The importance of non-dioxin-like PCBs in the context of the observed effect is uncertain because of the blending with the more potent dioxin-like PCBs. Previously, a controlled rat perinatal exposure study with individual, purity-controlled, non-dioxin-like congeners (PCB52, PCB138, or PCB180) was set up. Impaired motor coordination, motor activity, and learning has been reported for the offspring at an age of approximately 4 months. Here, we report on the gene expression responses that have been observed in the blood of the same animals. ANOVA analysis called 1412 genes differentially expressed 4 months after the PCB treatment was stopped. Subsequently, each PCB exposure condition was compared to the corresponding vehicle control using a fold change analysis. The gene lists contained between 82 and 348 differentially expressed genes. Expression patterns were complex with sets of differentially expressed genes being specific for a particular PCB exposure and other sets in common between several exposure conditions. Thirty-two genes were differentially expressed under all conditions. Bioinformatic overrepresentation analysis identified enriched biological terms such as lipid metabolism, molecular transport, small molecule biochemistry, and cell signaling and proliferation. Gene lists were particularly enriched for nervous system development and function ontology. In conclusion, we have documented for the first time differential gene expression in a well-controlled animal study that reported behavioral effects of purity-controlled individual non-dioxin-like PCBs.