The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi,China; Graduate School of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.
Graduate School of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China; Clinical Laboratory, The People's Hospital of Baise, Baise 530000, Guangxi, China.
Toxicol In Vitro. 2023 Oct;92:105658. doi: 10.1016/j.tiv.2023.105658. Epub 2023 Aug 6.
Aluminum chloride (AlCl) exposure is pervasive in our daily lives. Numerous studies have demonstrated that exposure to AlCl can lead to male reproductive toxicity. However, the precise mechanism of action remains unclear. The objective of this study is to investigate the mechanism of aluminum-induced toxicity by analyzing the alterations in the global transcriptome gene profile of mouse spermatocytes (GC-2spd cells) exposed to AlCl. GC-2spd cells were exposed to concentrations of 0, 1, 2, and 4 mM AlCl, and high-throughput mRNA-seq was performed to investigate the changes in the transcriptome after exposure to 4 mM AlCl. Our findings indicate that exposure to AlCl led to an increase in oxidative stress, disrupted glutathione metabolism, reduced cell viability, and altered gene expression in mouse spermatocytes. Gene enrichment analysis revealed that the differentially expressed genes (DEGs) were associated with various biological functions such as mitochondrial inner membrane, response to oxidative stress. Furthermore, these DEGs were found to be enriched in pathways including proteasome, glutathione metabolism, oxidative phosphorylation, and Hif-1 signaling pathway. Real-time PCR and western blot were employed to validate the expression alterations of pivotal genes, and the outcomes exhibited concordance with the mRNA-seq findings. This study provides a theoretical basis for revealing the potential mechanism of male reproductive toxicity caused by aluminum exposure.
氯化铝（AlCl）在我们的日常生活中无处不在。大量研究表明，接触 AlCl 可导致男性生殖毒性。然而，其确切的作用机制尚不清楚。本研究旨在通过分析氯化铝暴露的小鼠精母细胞（GC-2spd 细胞）的全转录组基因谱的变化，来研究铝诱导毒性的机制。GC-2spd 细胞分别暴露于 0、1、2 和 4mM AlCl，然后进行高通量 mRNA-seq，以研究暴露于 4mM AlCl 后转录组的变化。我们的研究结果表明，暴露于 AlCl 可导致氧化应激增加、谷胱甘肽代谢紊乱、细胞活力降低以及小鼠精母细胞基因表达改变。基因富集分析表明，差异表达基因（DEGs）与各种生物学功能相关，如线粒体内膜、对氧化应激的反应。此外，这些 DEGs 富集于蛋白酶体、谷胱甘肽代谢、氧化磷酸化和 Hif-1 信号通路等途径中。实时 PCR 和 Western blot 用于验证关键基因的表达变化，结果与 mRNA-seq 结果一致。本研究为揭示铝暴露引起男性生殖毒性的潜在机制提供了理论依据。
