Oral exposure of pubertal male mice to endocrine-disrupting chemicals alters fat metabolism in adult livers

Abstract

The potential for the exposure of humans and wildlife to environmental endocrine-disrupting chemicals (EDCs) has been increasing. Risk assessment for such EDCs is primarily based on detecting the main endpoints related to the endocrine and reproductive systems, while the effects on glucose and fat metabolism have only received limited attention. In this study, pubertal male C57BL/6J mice were orally administered 10 mg/kg body weight cypermethrin (CYP), 100 mg/kg body weight atrazine (ATZ), and 0.1 mg/kg body weight 17α-ethynyestradiol (EE2) for 4 weeks and then switched to a high-energy diet (HD) for 8 weeks. The body weight gain in the EDC-treated groups was lower than that in the control group during exposure and then tended to show values similar to the HD group. The epididymal fat weight, cell size and serum triacylglycerol (TG) and total cholesterol (TCH) levels in the EDC-HD groups were lower than those in the HD group. The transcription of genes related to glycolytic and gluconeogenic processes in the liver was affected by EDC exposure. Furthermore, the expression levels of transcriptional factors including PPARα, PPARγ, and SREBP1C and their target genes related to fatty acid synthesis and oxidation in the liver were also influenced by early life EDC administration. The results showed that early-life-stage exposure to high doses of various environmental EDCs affected the homeostasis of glucose and fatty acid metabolism in the livers of adult male mice.

Sublethal health effects in laboratory rodents from environmentally relevant exposures to oil sands contaminants

“…These results agree with those of Rogers et al , who observed increased relative liver, kidney, and spleen weights in rats exposed to naphthenic acids from oil sands tailings. Increased masses of these organs in animals exposed to endocrine disruptors have been attributed to edema or histopathological alterations possibly mediated by metabolic dysregulation . However, the relatively low doses of contaminants used in the present study suggest that the changes in scaled liver index and scaled kidney index are from physiological responses to pollutant exposure such as the activation of detoxifying metabolic routes , rather than from pathological changes, even though we did not detect increased ethoxyresorufin O ‐deethylase induction.…”

“…We consider that differences among groups for body condition at the end of the experiment, especially the increased body condition of the metals þ alkyl-PAHs group compared with controls, are confounded by the fact that mice exposed to alkyl-PAHs and metals þ alkyl-PAHs had relatively heavier livers, spleens, and kidneys, thus resulting in an apparent, but not truly better, body condition. However, exposure to low dosages of endocrine-disrupting chemicals can cause slight increases in body weight through disruption of normal homeostatic controls of adipogenesis and energy balance, whereas weight loss occurs after higher doses of exposure along with other signs of systemic toxicity [60,61]. The present study's hypothesis is partially supported by the results of Tête et al [62] in wild mice captured along a metal pollution gradient, who found that scaled mass index increased with Cd concentrations in both liver and kidneys of animals living in lightly and moderately polluted areas, whereas the relationship became inverted for animals trapped in highly polluted sites.…”

Dietary β‐glucan modulate haematological parameters, cytokines and gene expression in TLR and ERK pathways of rainbow trout ( Oncorhynchus mykiss ) during infection by Aeromonas salmonicida

“…These reagent kits have been validated in published papers for fish (Du et al, 2015;Jia, Cao, Xu, Jeney, & Yin, 2012;Jin et al, 2015). These reagent kits have been validated in published papers for fish (Du et al, 2015;Jia, Cao, Xu, Jeney, & Yin, 2012;Jin et al, 2015).…”

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

“…Recent study showed that ATZ also affects DNA methylation in plants (38). In mammals, ATZ exposure affects many tissues, including testes (39–42), ovaries (43–47), brain (48,49), liver (50–54) and the presence of low dose metabolites of ATZ is associated with low birth weight in human (55). …”