Abstract
BACKGROUND: Evaluation of the combined effects of endocrine-disrupting chemicals and dietary factors provides critical information for cumulative health risk assessment. Herein, we investigated the effects of cadmium (Cd) exposure and high fructose (HFr) diet on metabolic and reproductive health in female mice. METHODS: Female CD-1 mice were exposed to cadmium chloride (CdCl(2)) (0.0 ppm, 0.5 ppm, or 5.0 ppm) in drinking water with or without 59 % high fructose (HFr) diet for 7.5 weeks. Body composition, serum chemistry, hepatic lipid composition and gene expression were evaluated for metabolic disruption. To assess reproductive health, steroid hormones and estrous cyclicity were measured. RESULTS: The combination of Cd and HFr diet did not alter body composition, adipokines, nor circulating lipids. Conversely, this combination exacerbated the independent Cd- and HFr diet-induced reductions in serum IL-1β. HFr diet drove the bulk of the effects on surveyed metabolic endpoints irrespective of Cd exposure. However, both Cd and HFr diet independently reduced serum estradiol and interfered with estrous cyclicity. CONCLUSION: These results suggest that, at least for metabolic outcomes in females, HFr diet is the main driver of adverse effects. While limited interaction between these exposures was present, both stressors equally disrupted reproductive health endpoints in female mice.