Effects of cross-fostering and developmental exposure to mixtures of environmental contaminants on hepatic gene expression in prepubertal 21 days old and adult male Sprague-Dawley rats
- Language of the publication
- English
- Date
- 2019-02-11
- Type
- Article
- Author(s)
- Desaulniers, D.
- Khan, N.
- Cummings-Lorbetskie, C.
- Leingartner, K.
- Xiao, G-H.
- Williams, A.
- Yauk, C.L.
- Publisher
- Taylor and Francis
Abstract
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 cross-fostered 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.
Plain language summary
Health Canada is responsible for evaluating the health risks posed by environmental pollutants, and other chemicals, to Canadians. Health Canada scientists had previously investigated the link between non-chemical stressors and susceptibility to the adverse effects of exposure to environmental chemicals (EC). Results demonstrated that cross-fostering of rat pups (rat pups adopted at birth by a nursing mother) was a stressful event that increased the adverse effects of ECs on hormonal stress-responses in the grown adults. The current study investigates effects of cross-fostering and developmental exposure to mixtures of EC on gene expression changes in the liver, with the intent of identifying changes that could be associated with health risks. Low concentrations of mixtures of EC, with compositions simulating the exposure profile identified in surveys of the maternal blood of Northern Canadians, were administered to rats from pregnancy until 21 days after birth. The pups were thus exposed to EC in the womb and through milk from the mother. Some pups were cross-fostered (non-chemical stressful event), and at 21 days of age, or later during adulthood, gene expression in the liver was compared to non-cross-fostered animals. Exposure to the mixture of EC altered the expression of genes associated with detoxication and energy regulation functions of the liver in both age groups, but with different mechanisms being affected at day 21 versus older animals. Cross-fostering modulated the effects of the EC mixture and surprisingly, also modulated the energy functions in control rats not exposed to the chemicals. Changes in the liver’s response to EC associated with cross-fostering, along with changes to the hormonal stress-responses identified in previous work, support the hypothesis that non-chemical stressors can modify the toxicity of exposure to EC. Sources and magnitudes of stress that can modulate effects of EC on human health will be investigated further.
Subject
- Health,
- Health and safety