| 摘要: |
| 为探索内分泌干扰物DEHP在母鼠怀孕期间暴露后对子鼠生殖系统的影响,为DEHP诱导雄性生殖毒性机制提供生物信息学参考。采用美国国立生物技术信息中心的GEO(Gene expression omnibus)数据库筛选DEHP组与对照组差异表达的mRNA并进行GO和 KEGG通路富集分析。使用STRING数据库、Cytoscape软件对差异表达基因构建蛋白质互作网络(PPI),并根据CytoHubba插件的MCC算法筛选出前十个关键基因。利用GSEA软件对基因集进行基因集富集分析(Gene set enrichment analysis,GSEA),筛选在DEHP暴露后有统计学意义的基因集。本研究首先基于差异表达筛选出Cyp51,Sqle,Sc5d,Fdps,Dhcr7,Acss2,Insig1,Idi1,Scd1等关键基因。富集分析显示这些mRNA可能通过影响胆固醇合成代谢、类固醇合成代谢等相关途径发挥作用。此外,GSEA分析结果也清楚地表明DEHP暴露后会诱导小鼠胆固醇合成、mTORC1通路、雄性激素响应相关途径发生改变。研究发现,在母鼠怀孕期间暴露DEHP可能会影响雄性子鼠mTORC1通路,胆固醇合成相关途径引起小鼠雄性激素紊乱导致精子发生障碍,干扰小鼠生殖系统。 |
| 关键词: 邻苯二甲酸二乙己基酯 基因富集分析 睾丸 生殖毒性 内分泌干扰物 |
| DOI：10.12113/202403004 |
| 分类号:Q811.4 |
| 文献标识码:A |
| 基金项目: |
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| Exploring the mechanism of DEHP induced male reproductivedevelopment disorders based on GEO chip data |
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ZHOU Jinggang1,2, HE Qingzhi1,2
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(1.College of Intelligent Medicine and Biotechnology,Guilin Medical University,Guilin 541199,China;2.Key Laboratory of Molecular Medical Engineering, Education Department of Guangxi Zhuang Autonomous Region,Guilin Medical University ,Guilin 541199,China)
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| Abstract: |
| To explore the effects of endocrine disruptor DEHP on the reproductive system of offspring rats after exposure during pregnancy, and provide bioinformatics references for the mechanism of DEHP-induced male reproductive toxicity.The GEO (Gene expression omnibus) database of the National Center for Biotechnology Information is used to screen differentially expressed mRNAs between the DEHP group and the control group, and GO and KEGG pathway enrichment analysis are performed. The differentially expressed genes are mapped into a PPI protein interaction network using the STRING database and Cytoscape software, and the top ten key genes are selected based on the MCC algorithm of the CytoHubba plugin. The gene set enrichment analysis (GSEA) is performed using GSEA software to screen gene sets with statistically significant differences after DEHP exposure.This study first screens out key genes such as Cyp51,Sqle,Sc5d,Fdps,Dhcr7,Acss2,Insig1,Idi1,Scd1based on differential expression. Enrichment analysis shows that these mRNAs may play a role by affecting cholesterol synthesis and metabolism, steroid synthesis and metabolism, and other related pathways. In addition, the results of GSEA analysis also clearly shows that DEHP exposure induces changes in cholesterol synthesis, mTORC1 pathway, and male hormone response-related pathways in mice.This study finds through bioinformatics that exposure to DEHP during pregnancy in female mice may affects the mTORC1 pathway and cholesterol synthesis-related pathways in male offspring, causing male hormone disorders in mice, resulting in impaired spermatogenesis and interfering with the reproductive system of mice. |
| Key words: DEHP Gene enrichment analysis Testis Reproductive toxicity Endocrine disruptor |
