Cadmium chloride and erectile dysfunction: integrative evidence from network toxicology, Mendelian randomization, and in vitro validation

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Background In recent years, heavy metal exposure has been increasingly implicated in the onset and progression of various diseases. However, the relationship between heavy metal exposure and male erectile function remains insufficiently understood. This study aimed to investigate the association between cadmium chloride (CdCl 2 ) and erectile dysfunction (ED), and to explore the underlying molecular mechanisms. Methods An integrated analytical framework was established to elucidate the potential link between cadmium chloride and ED. Key cadmium-ED related genes were first identified through comprehensive analyses using multiple databases, including PubChem, TargetNet, GeneCards, and STRING. Subsequently, Mendelian randomization (MR) analysis was conducted to assess the causal relationship between cadmium associated genes and ED. Finally, in vitro experiments were carried out to examine the effects of varying concentrations of CdCl 2 on human umbilical vein endothelial cells (HUVECs), focusing on alterations in cell viability and gene expression. Results Network toxicology analysis identified estrogen receptor 2 ( ESR2 ) as a key gene mediating the link between cadmium chloride and ED. MR analysis demonstrated that increased ESR2 expression was causally associated with a higher risk of ED. In vitro experiments further showed that CdCl 2 exposure led to a concentration- and time-dependent reduction in HUVEC viability, accompanied by upregulation of ESR2 expression. Conclusion CdCl 2 exposure may be associated with the onset and progression of erectile dysfunction, and its potential effects may involve multiple aspects, including vascular endothelial dysfunction, disruption of endocrine homeostasis, and abnormal ESR2 related signaling.

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