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. 2024 Jul 10;25(14):7586.
doi: 10.3390/ijms25147586.

Transcriptomic and Epigenomic Responses to Cortisol-Mediated Stress in Rainbow Trout (Oncorhynchus mykiss) Skeletal Muscle

Daniela Aravena-Canales  1   2 , Valentina Valenzuela-Muñoz  2   3   4 , Cristian Gallardo-Escarate  2   4 , Alfredo Molina  1   2   5 , Juan Antonio Valdés  1   2   5
Affiliations

Transcriptomic and Epigenomic Responses to Cortisol-Mediated Stress in Rainbow Trout (Oncorhynchus mykiss) Skeletal Muscle

Daniela Aravena-Canales et al. Int J Mol Sci. .

Abstract

The production and release of cortisol during stress responses are key regulators of growth in teleosts. Understanding the molecular responses to cortisol is crucial for the sustainable farming of rainbow trout (Oncorhynchus mykiss) and other salmonid species. While several studies have explored the genomic and non-genomic impacts of cortisol on fish growth and skeletal muscle development, the long-term effects driven by epigenetic mechanisms, such as cortisol-induced DNA methylation, remain unexplored. In this study, we analyzed the transcriptome and genome-wide DNA methylation in the skeletal muscle of rainbow trout seven days after cortisol administration. We identified 550 differentially expressed genes (DEGs) by RNA-seq and 9059 differentially methylated genes (DMGs) via whole-genome bisulfite sequencing (WGBS) analysis. KEGG enrichment analysis showed that cortisol modulates the differential expression of genes associated with nucleotide metabolism, ECM-receptor interaction, and the regulation of actin cytoskeleton pathways. Similarly, cortisol induced the differential methylation of genes associated with focal adhesion, adrenergic signaling in cardiomyocytes, and Wnt signaling. Through integrative analyses, we determined that 126 genes showed a negative correlation between up-regulated expression and down-regulated methylation. KEGG enrichment analysis of these genes indicated participation in ECM-receptor interaction, regulation of actin cytoskeleton, and focal adhesion. Using RT-qPCR, we confirmed the differential expression of lamb3, itga6, limk2, itgb4, capn2, and thbs1. This study revealed for the first time the molecular responses of skeletal muscle to cortisol at the transcriptomic and whole-genome DNA methylation levels in rainbow trout.

Keywords: Oncorhynchus mykiss; RNA-seq; WGBS; cortisol; skeletal muscle.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Assessment of physiological response to stress: cortisol (a), glucose (b), and lactate (c) in plasma were assessed in juvenile rainbow trout kept under cortisol and control 3 h and 7 days after treatment. The results are expressed as means and + standard errors (n = 5 per treatment). Differences between control and stress groups are shown in * p < 0.05, ** p < 0.01, *** p < 0.005.
Figure 2
Figure 2
Bubble plot showing enriched KEGG pathways, resulting from the DEGs between control and cortisol groups.
Figure 3
Figure 3
Genome profile of CpG methylation. (a) Relative level of methylated cytosines (CG, CHG, and CHH) in experimental groups. (b) Chromosome distribution of hyper- and hypo-differentially methylated regions. (c) Number of DMRs in different genomics contexts.
Figure 4
Figure 4
Bubble plot showing enriched KEGG pathways resulting from the DMGs between control and cortisol groups.
Figure 5
Figure 5
RT-qPCR validation of DEGs and DMGs between control and cortisol treatments. Genes selected for the RT-PCR validation were lamb3, itga6, limk2, itgb4, capn2, and thbs1. For RNA-seq, in White, “#” indicates a log2 fold change ≥2.0 and FDR <0.05. For RT-qPCR, in black, relative expression was normalized against fau and actβ. The results are expressed as means and + standard errors (n = 5 per treatment). Differences between control and cortisol groups are shown in * p < 0.05 and ** p < 0.01.
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