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The effects of cadmium and high fructose diet on metabolic and reproductive health in female CD-1 mice.

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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 (CdCl2) (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.

Impact/Purpose

Independently, exposures to either environmental contaminants or various nutritional factors cause significant health outcomes. However, research investigating both stressors together (e.g., cumulative impacts) is limited, with even fewer studies available that demonstrate the biological underpinnings of such potential interactions in the environment (Vesterinen et al., 2017). To help fill this research gap, we examined the effects of a relatively low concentration of Cd in the drinking water and high fructose (HFr) diet on endpoints related to metabolic and reproductive health in female CD-1 mice. As such, we describe their impacts both individually and in combination on body composition, circulating hormones and serum chemistry, liver lipid composition and gene expression, and estrous cyclicity.

Citation

Adams, V., J. Dye, M. Narotsky, M. Moore, H. Nguyen, A. Sasser, K. Das, L. Strader, Joseph Pancras, D. Jenkins-Hill, C. Davis, W. Williams, R. Grindstaff, W. Padgett, Chris Lau, AND C. Miller. The effects of cadmium and high fructose diet on metabolic and reproductive health in female CD-1 mice. Elsevier Science Ltd, New York, NY, 206:115726, (2025). [DOI: 10.1016/j.fct.2025.115726]

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DOI: The effects of cadmium and high fructose diet on metabolic and reproductive health in female CD-1 mice.
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Last updated on March 02, 2026
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