Integrated transcriptome and metabolomic analyses uncover the mechanism of cadmium-caused mouse spermatogonia apoptosis via inducing endoplasmic reticulum stress

Cadmium (Cd) is a well-recognized male reproductive toxicant that can cause testicular germ cell apoptosis. However, the underlying mechanism needs investigation. CG-1 mouse spermatogonia (spg) cells were treated with 20 μM cadmium chloride (CdCl2) for 24 h. Cell apoptosis was measured, and the expressions of key genes and protein biomarkers involved in endoplasmic reticulum (ER) stress were detected, respectively. Untargeted metabolomics was performed to identify different metabolites, and transcriptome analysis was conducted to screen differentially expressed genes (DEGs). Our results indicated that CdCl2 exposure caused cell apoptosis, and DEGs were involved in several apoptosis-related pathways. Moreover, CdCl2 exposure apparently increased the mRNA and protein expressions levels of both GRP78 and ATF6α, disrupting the expression of various metabolites, particularly amino acids. Conclusively, our study reveals the pathway of CdCl2 toxicity on mouse spg, providing a deep understanding of CdCl2-induced testicular toxicity. •CdCl2 damages testicular spermatogonia.•CdCl2 triggers spermatogonia apoptosis.•CdCl2 induces ER stress in spermatogonia.•CdCl2 disrupts the amino acid metabolism of spermatogonia.