Abstract

Understanding heat stress physiology and identifying reliable biomarkers are paramount for developing effective management and mitigation strategies. However, little is known about the molecular mechanisms underlying thermal tolerance in animals. In an experimental model of Sprague–Dawley rats subjected to temperatures of 22 ± 1°C (control group; CT) and 42°C for 30 min (H30), 60 min (H60), and 120 min (H120), RNA-sequencing (RNA-Seq) assays were performed for blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120). A total of 53, 1,310, and 1,501 differentially expressed genes (DEGs) were significantly identified in the blood (P < 0.05 and |fold change (FC)| >2), liver (P < 0.01, false discovery rate (FDR)–adjusted P = 0.05 and |FC| >2) and adrenal glands (P < 0.01, FDR-adjusted P = 0.05 and |FC| >2), respectively. Of these, four DEGs, namely Junb, P4ha1, Chordc1, and RT1-Bb, were shared among the three tissues in CT vs. H120 comparison. Functional enrichment analyses of the DEGs identified in the blood (CT vs. H120) revealed 12 biological processes (BPs) and 25 metabolic pathways significantly enriched (FDR = 0.05). In the liver, 133 BPs and three metabolic pathways were significantly detected by comparing CT vs. H30, H60, and H120. Furthermore, 237 BPs were significantly (FDR = 0.05) enriched in the adrenal glands, and no shared metabolic pathways were detected among the different heat-stressed groups of rats. Five and four expression patterns (P < 0.05) were uncovered by 73 and 91 shared DEGs in the liver and adrenal glands, respectively, over the different comparisons. Among these, 69 and 73 genes, respectively, were proposed as candidates for regulating heat stress response in rats. Finally, together with genome-wide association study (GWAS) results in cattle and phenome-wide association studies (PheWAS) analysis in humans, five genes (Slco1b2, Clu, Arntl, Fads1, and Npas2) were considered as being associated with heat stress response across mammal species. The datasets and findings of this study will contribute to a better understanding of heat stress response in mammals and to the development of effective approaches to mitigate heat stress response in livestock through breeding.

Highlights

  • Heat stress refers to the sum of the nonspecific physiological responses of the body to high ambient temperature (Dikmen and Hansen, 2009)

  • Through the exploration of the transcriptome profile, further understanding of the coping mechanisms under heat stress challenges from the perspective of genetic regulation is essential for in-depth explaining of thermo-tolerance and breeding of heat-tolerant varieties

  • The quality of the 28 RNA-Seq data generated from blood, liver, and adrenal gland samples in the CT and H120 groups was reported by Dou et al (2020) and showed an average of 9.46 Gb paired-end clean reads for each sample, with high quality (GC content: 50.81%, Q20: 95.06%, and Q30: 89.10%)

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Summary

Introduction

Heat stress refers to the sum of the nonspecific physiological responses of the body to high ambient temperature (Dikmen and Hansen, 2009). The definitions (Armstrong, 1994; De Rensis et al, 2015) and THI values (Bohmanova et al, 2007) tend to vary across studies and environmental conditions (e.g., geographic location, physical size, and the different equations), and THI can only be used as a rough indicator for assessing heat stress (Polsky and von Keyserlingk, 2017) In this context, various studies have focused on evaluating the effects of heat stress in humans and other animals (e.g., cattle, pig, and sheep) from the perspective of physiological measures to assess body coping mechanisms when exposed to different environmental challenges. Physiological measures can describe the health and biological status at a given environmental condition, they fail to constitute a gold standard due to their susceptibility to different detection methods and physiological conditions

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