Dynamic and systemic regulatory mechanisms in rainbow trout (Oncorhynchus mykiss) in response to acute hypoxia and reoxygenation stress

Hypoxia frequently occurs in natural aquatic systems and aquaculture environments due to extreme climate fluctuations, high-density farming, environmental pollution and global warming, resulting in serious ecological damage and enormous economic losses. Rainbow trout (Oncorhynchus mykiss), a key economic fish species worldwide, is extremely sensitive to hypoxia. However, the regulatory mechanisms in response to environmental hypoxia and reoxygenation stress remain unknown. Herein, rainbow trout liver transcriptomes and biochemical parameters were investigated in response to hypoxia for different durations (3, 12 and 24 h), reoxygenation (hypoxia for 24 h followed by reoxygenation for 3 h) and normoxia to highlight dynamic changes in molecular regulation and oxidative stress. In RNA-seq analysis, 5906 differentially expressed genes, two significantly expressed gene sets (profiles 10 and 12) and two hypoxia specific modules (MEgreen and MEturquoise) were screened by differential expression analysis, short time-series expression miner (STEM) and weighted gene co-expression network analysis (WGCNA), respectively. The intersection of the above analyses further identified several key hub genes related to hypoxia, including hif-1 alpha, epo, igfbp1, ddit4, pck1, g6pc, cyp1a1 and dusp1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed different metabolic strategies at different stress stages; signal transmission and protein synthesis process were strongly influenced by hypoxia. The immune system was inhibited, and a switch from programmed to pathological cell death was observed from hypoxia for 12 h to 24 h. After reoxygenation for 3 h, mitochondrial oxidative phosphorylation was strongly activated to provide more cellular ATP. Enzymatic and non-enzymatic antioxidant systems clearly coordinate to alleviate oxidative stress injury caused by hypoxia. This study reveals dynamic and systemic regulatory mechanisms in rainbow trout liver, and lays a foundation for further study on the molecular mech-anisms governing responses to environmental hypoxia and reoxygenation stress.