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.

Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells

“…Particularly enriched gene lists in this study included genes of the nervous system development and function ontology. Besides that, enriched pathways included lipid metabolism, molecular transport, small molecule biochemistry, and cell signaling and proliferation [49]. We have to keep in mind, that in this study PBMCs of other species were used and the time of the exposure was in utero.…”

In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels

“…We were unable to identify studies in which long lasting changes in lipid metabolism outcomes were analyzed following developmental exposures to PCB. However, in four-month-old rats exposed perinatally to non-dioxin-like PCBs changes in gene expression in blood were significantly enriched for lipid metabolism [38].…”

Lactational exposure to low levels of the six indicator non-dioxin-like polychlorinated biphenyls induces DNA damage and repression of neuronal activity, in juvenile male mice

“…One of the closest study design to our work is the gene expression profiles in the peripheral blood of rats exposed to individual NDL congeners (PCBs 52, 138 and 180) at 1 mg/kg during gestation and lactation (De Boever et al, 2013). The authors have found differentially expressed genes belonging to terms involved in lipid metabolism, molecular transport, small molecular biochemistry and cell signaling and proliferation in the peripheral blood of PCB-exposed rats.…”