Di-san junyi daxue xuebao (Jan 2021)
Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways
Abstract
Objective To explore the possible key pathways in the male reproductive toxicity induced by exposure to low-dose bisphenol A (BPA). Methods BPA-related genes were screened based on Comparative Toxicogenomics Database (CTD). Functional enrichment analysis was used for these genes to explore the possible pathways and identify the key genes in related pathways. Mouse spermatogonia cell line GC-2 cells were treated with BPA at a final concentration of 0 (DMSO control group), 20, 40 and 80 μmol/L for 72 h. Then the changes of cell morphology and apoptotic rate were observed. The mRNA and protein expression levels of the obtained key genes were detected by RT-qPCR and Western blotting, respectively. Results A total of 1 460 BPA-related genes were screened out from the CTD database. Gene Ontology (GO) enrichment analysis showed that these genes were significantly enriched in molecular biological processes, such as reproductive system development and reproductive structure development, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that they were significantly enriched in HIF-1 and PI3K-Akt signaling pathways (P < 0.01). Visual analysis showed that the key genes in the pathway were HIF-1α, PKC and P300/CBP, and PI3K, JAK, P53 and BCL-2. The apoptotic rate of GC-2 cells exposed to BPA was significantly increased in a dose-dependent manner (P < 0.05). Compared with the control cells, the mRNA expression levels of PI3K and JAK were significantly down-regulated, while those of P53 and BCL-2 were up-regulated (P < 0.05). The protein levels of PI3K and BCL-2 were obviously down-regulated, while that of P53 up-regulated (P < 0.05). Conclusion The PI3K-Akt signaling pathway may play an important role in the process of GC-2 cell apoptosis induced by low-dose BPA exposure.
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