The notion that adverse health effects produced by exposure to environmental contaminants (EC) may be modulated by the presence of non-chemical stressors is gaining attention. Previously, our lab demonstrated that cross-fostering (adoption of a litter at birth) acted as a non-chemical stressor that amplified the influence of developmental exposure to EC on the glucocorticoid stress-response in adult rats. Using liver from the same rats, the aim of the current study was to investigate whether cross-fostering might also modulate EC-induced alterations in hepatic gene expression profiles. During pregnancy and nursing, Sprague-Dawley dams were fed cookies laced with corn oil (control, C) or a chemical mixture (M) composed of polychlorinated biphenyls (PCB), organochlorine pesticides (OCP), and methylmercury (MeHg), at 1 mg/kg/day. This mixture simulated the contaminant profile reported in maternal human blood. At birth, some control and M treated litters were crossfostered to form two additional groups with different biological/nursing mothers (CC and MM). The hepatic transcriptome was analyzed by DNA microarray in male offspring at postnatal days 21 and 78–86. Mixture exposure altered the expression of detoxification and energy metabolism genes in both age groups, but with different sets of genes affected at day 21 and 78–86. Cross-fostering modulated the effects of M on gene expression pattern (MM vs M), as well as expression of energy metabolism genes between control groups (CC vs C). In conclusion, while describing short- and long-term effects of developmental exposure to EC on hepatic transcriptomes, these cross-fostering results further support the consideration of non-chemical stressors in EC risk assessments.
Overall design: Dams (Sprague Dawley, rats) were treated during the gestation and lactation period, and eight male pups per treatment group were investigated. RNA from pairs of rats in the same treatment group was randomly pooled together and thus each treatment group was represented by four microarrays. To investigate mixture effects, five treatment groups were not cross-fostered and remained with their birth mothers (C, 0.5M, M, AhR, and 0.5MAhR), whereas four groups were compared to investigate effects of cross-fostering (CC vs C, and MM vs M). The effects of developmental exposure to the chemical mixtures and effects of cross-fostering were investigated in rats at two time points, at 21 days of age, and at 78-86 days of age. There were 72 samples included in the final analysis using a two-colour experiment (e.g., Cy5/Cy3) microarray design
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