Transcriptome Revealed Exposure to the Environmental Ammonia Induced Oxidative Stress and Inflammatory Injury in Spleen of Fattening Pigs

SIMPLE SUMMARY: Ammonia is a major environmental pollutant. Previous estimates of ammonia emissions have focused on livestock sources in agricultural systems. Livestock continues to be the main source of ammonia emissions. Exposure to high concentrations of ammonia can cause varying degrees of damage to tissues and organs. However, the damage of ammonia exposure to the spleen of pigs in the fattening pigs is unknown. Therefore, the aim of this study was to explore the mechanism at the gene level of exogenous ammonia-induced spleen toxicity by enzyme-linked immunosorbent assay (ELISA), spleen histomorphological observation, and transcriptome technology. The results showed that ammonia exposure led to oxidative stress, activation of inflammatory pathways, and splenic injury. In addition, the genes that encode histone methyltransferase were found to be significantly upregulated. Therefore, histone methylation may be the epigenetic mechanism of splenic poisoning induced by ammonia. Our findings provide a novel direction for exploring the underlying molecular mechanisms of ammonia toxicity. ABSTRACT: Ammonia is one of the major environmental pollutants that seriously threaten human health. Although many studies have shown that ammonia causes oxidative stress and inflammation in spleen tissue, the mechanism of action is still unclear. In this study, the ammonia poisoning model of fattening pigs was successfully established. We examined the morphological changes and antioxidant functions of fattening pig spleen after 30-day exposure to ammonia. Effects of ammonia in the fattening pig spleen were analyzed from the perspective of oxidative stress, inflammation, and histone methylation via transcriptome sequencing technology (RNA-seq) and real-time quantitative PCR validation (qRT-PCR). We obtained 340 differential expression genes (DEGs) by RNA-seq. Compared with the control group, 244 genes were significantly upregulated, and 96 genes were significantly downregulated in the ammonia gas group. Some genes in Gene Ontology (GO) terms were verified and showed significant differences by qRT-PCR. The KEGG pathway revealed significant changes in the MAPK signaling pathway, which is strongly associated with inflammatory injury. To sum up, the results indicated that ammonia induces oxidative stress in pig spleen, activates the MAPK signaling pathway, and causes spleen necrosis and injury. In addition, some differential genes encoding epigenetic factors were found, which may be involved in the response mechanism of spleen tissue oxidative damage. The present study provides a transcriptome database of ammonia-induced spleen poisoning, providing a reference for risk assessment and comparative medicine of ammonia.