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

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.