Integrated transcriptome and metabolomic analyses uncover the mechanism of cadmium-caused mouse spermatogonia apoptosis via inducing endoplasmic reticulum stress.
Jie WuQizi YinYi WangRong WangWenjing GongYihang ChenMingming ZhangYehao LiuYanli JiPublished in: Reproductive toxicology (Elmsford, N.Y.) (2024)
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 (CdCl 2 ) 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 CdCl 2 exposure caused cell apoptosis, and DEGs were involved in several apoptosis-related pathways. Moreover, CdCl 2 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 CdCl 2 toxicity on mouse spg, providing a deep understanding of CdCl 2 -induced testicular toxicity.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- amino acid
- endoplasmic reticulum
- cell proliferation
- genome wide
- oxidative stress
- binding protein
- mass spectrometry
- heavy metals
- ms ms
- cell cycle arrest
- germ cell
- poor prognosis
- diabetic rats
- protein protein
- gene expression
- cell death
- single cell
- high throughput
- drug induced
- dna methylation
- bioinformatics analysis
- signaling pathway
- high glucose
- rna seq
- newly diagnosed