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

Adams VR, Victoria R Adams, Janice A Dye, Dye JA, Narotsky MG, Micheal G Narotsky, Moore ML, Makala L Moore, Nguyen HH, Helen H Nguyen, Aubrey L Sasser, Sasser AL, Das KP, Kaberi P Das, Lillian F Strader, Strader LF, Joseph P Pancras, Pancras JP, Hill D, Donna Hill, Chloe Davis, Davis C, Williams WC, Wanda C Williams, Rachel D Grindstaff, Grindstaff RD, William T Padgett, Padgett WT, Christopher Lau, Lau C, Colette N Miller, Miller CN
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2025 · vol. 206 , pp. 115726 · doi:10.1016/j.fct.2025.115726 · PMID:40914447 · PMC13034443
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Female CD-1 mice exposed to cadmium and a high fructose diet showed that the diet primarily drove metabolic disruptions while both exposures equally reduced estradiol and interfered with estrous cyclicity.

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This study investigated the combined impact of cadmium exposure and a high fructose diet on metabolic and reproductive health in female CD-1 mice over a 7.5-week period. Researchers observed that while the high fructose diet primarily drove adverse metabolic changes, both cadmium and the diet independently reduced serum estradiol levels and disrupted normal estrous cyclicity. The findings indicate that these environmental and dietary stressors equally impair reproductive endpoints despite limited interaction in metabolic outcomes. Relevance to endometriosis: The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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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 (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.
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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 (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.

Keywords

Cadmium; Estrous cycle; Heavy metals; High fructose diet; Metabolic dysfunction-associated fatty liver disease. Published by Elsevier Ltd. Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Figures

References

- - Abdel-Badeea WIE, Abdel-Wahab A, Mahmoud AA, Abdel-Razik AH, Attia EZ, Abdelmohsen UR, & Hassanin KMA (2025). Syzygium cumini Fruit Extract and Quercetin Ameliorate Cadmium-Induced Ovarian Apoptosis in Rats Via miRNA- 204 – 5p-Mediated Bcl- 2 Upregulation and Bax/Caspase 9/Caspase 3 Downregulation. Biol Trace Elem Res. 10.1007/s12011-025-04632-y - DOI - PMC - PubMed - - Baraskar K, Thakur P, Shrivastava R, & Shrivastava VK (2021). Female obesity: Association with endocrine disruption and reproductive dysfunction. Obesity Medicine, 28, 100375. 10.1016/j.obmed.2021.100375 - DOI MeSH terms Substances Grants and funding LinkOut - more resources Full Text Sources

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MeSH descriptors

Cadmium Cadmium Fructose Fructose Fructose Reproduction Reproduction Reproductive Health Animals Body Composition Body Composition Diet Estrous Cycle Estrous Cycle Female Liver Liver Liver Mice

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