Transcriptome-based analysis of the toxic effects of aluminum chloride exposure on spermatocytes.

Aluminum chloride (AlCl3) exposure is pervasive in our daily lives. Numerous studies have demonstrated that exposure to AlCl3 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 AlCl3. GC-2spd cells were exposed to concentrations of 0, 1, 2, and 4 mM AlCl3, and high-throughput mRNA-seq was performed to investigate the changes in the transcriptome after exposure to 4 mM AlCl3. Our findings indicate that exposure to AlCl3 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.

Cyclin-dependent kinase 7 gene silencing or knockout represses proliferation of ovarian cancer cells and the mechanism research / 肿瘤

Objective: To investigate the role of cyclin-dependent kinase 7 (CDK7) in the proliferation of ovarian cancer cells. Methods: The ovarian cancer cell lines OVCA433, TOV-112D and IGROVl were transfected with specific siRNA to downregulate the expression of CDK7 gene, then the cell proliferation viability was detected by CCK-8 method. The CDK7 gene in ovarian cancer HEY, OVCA420, OVCA433 and IGROVl cells was knocked out by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9 (Cas9) system, then the clone formation ability was detected by plate clone formation assay. The ovarian cancer TOV-112D, IGROV1, OVCA433, OVCAR8, OV90, SKOV3 and COV413B cells were treated with CDK7-inhibitor THZl, then the cell proliferation viability and clone formation ability were detected by CCK-8 method and clone formation assay, respectively. Furthermore, the expression level of CDK7 protein and the phosphorylation level of RNA polymerase n (RNAPolE) in IGROV1, OVCA433, SKOV3 and COV41 3B cells treated with THZl were analyzed by Western blotting. Results: The proliferation and clone formation abilities of various ovarian cancer cells were significantly decreased after CDK7 gene was silenced or knocked out (all P < 0.05). THZ1 repressed the proliferation and clon e formation of ovarian cancer cells, an d downregulated the expression of CDK7 and the phosphorylation of RNAPoln (all P < 0.05). Conclusion: CDK7 may promote the proliferation of ovarian cancer cells by regulating the phosphorylation of RNAPoln.