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Issue 3, 2020
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Complex epigenetic patterns in cerebellum generated after developmental exposure to trichloroethylene and/or high fat diet in autoimmune-prone mice

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Abstract

Trichloroethylene (TCE) is an environmental contaminant associated with immune-mediated inflammatory disorders and neurotoxicity. Based on known negative effects of developmental overnutrition on neurodevelopment, we hypothesized that developmental exposure to high fat diet (HFD) consisting of 40% kcal fat would enhance neurotoxicity of low-level (6 μg per kg per day) TCE exposure in offspring over either stressor alone. Male offspring were evaluated at ∼6 weeks of age after exposure beginning 4 weeks preconception in the dams until weaning. TCE, whether used as a single exposure or together with HFD, appeared to be more robust than HFD alone in altering one-carbon metabolites involved in glutathione redox homeostasis and methylation capacity. In contrast, opposing effects of expression of key enzymes related to DNA methylation related to HFD and TCE exposure were observed. The mice generated unique patterns of anti-brain antibodies detected by western blotting attributable to both TCE and HFD. Taken together, developmental exposure to TCE and/or HFD appear to act in complex ways to alter brain biomarkers in offspring.

Graphical abstract: Complex epigenetic patterns in cerebellum generated after developmental exposure to trichloroethylene and/or high fat diet in autoimmune-prone mice

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Article information


Submitted
05 Nov 2019
Accepted
12 Dec 2019
First published
13 Dec 2019

Environ. Sci.: Processes Impacts, 2020,22, 583-594
Article type
Paper

Complex epigenetic patterns in cerebellum generated after developmental exposure to trichloroethylene and/or high fat diet in autoimmune-prone mice

S. J. Blossom, S. B. Melnyk and F. A. Simmen, Environ. Sci.: Processes Impacts, 2020, 22, 583 DOI: 10.1039/C9EM00514E

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