双酚A致雄性生殖损害毒性通路的富集分析及关键凋亡信号通路的实验研究

袁文博; 刘文斌; 陈洪强; 柴子力; 张光辉; 曹佳

doi:10.16016/j.1000-5404.202009210

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双酚A致雄性生殖损害毒性通路的富集分析及关键凋亡信号通路的实验研究

专题报道:生殖损害和不良妊娠结局的危险因素研究 | 更新时间：2026-01-09

- 双酚A致雄性生殖损害毒性通路的富集分析及关键凋亡信号通路的实验研究
- Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways
- 第三军医大学学报 2021年43卷第1期页码：38-44
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家重点研发计划项目(2017YFC1002001);国家自然科学基金重点项目(81630087)
- DOI：10.16016/j.1000-5404.202009210
  中图分类号：
- 收稿：2020-09-24，
  
  纸质出版：2021-01-15
- 稿件说明：
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袁文博, 刘文斌, 陈洪强, 等. 双酚A致雄性生殖损害毒性通路的富集分析及关键凋亡信号通路的实验研究[J]. 第三军医大学学报, 2021,43(1):38-44.

Wenbo YUAN, Wenbin LIU, Hongqiang CHEN, et al. Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways[J]. Journal of Third Military Medical University, 2021, 43(1): 38-44.
袁文博, 刘文斌, 陈洪强, 等. 双酚A致雄性生殖损害毒性通路的富集分析及关键凋亡信号通路的实验研究[J]. 第三军医大学学报, 2021,43(1):38-44. DOI： 10.16016/j.1000-5404.202009210.

Wenbo YUAN, Wenbin LIU, Hongqiang CHEN, et al. Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways[J]. Journal of Third Military Medical University, 2021, 43(1): 38-44. DOI： 10.16016/j.1000-5404.202009210.

摘要

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)

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 (

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 (

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 (

0.05). The protein levels of PI3K and BCL-2 were obviously down-regulated

while that of P53 up-regulated (

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.

关键词

Keywords

references

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