Dou Jinhuan, Cánovas Angela, Brito Luiz F, Yu Ying, Schenkel Flavio S, Wang Yachun
Key Laboratory of Animal Genetics, Breeding and Reproduction, MARA, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
Department of Animal Biosciences, Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, Canada.
Front Genet. 2021 Apr 9;12:651979. doi: 10.3389/fgene.2021.651979. eCollection 2021.
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 ( < 0.05 and |fold change (FC)| >2), liver ( < 0.01, false discovery rate (FDR)-adjusted = 0.05 and |FC| >2) and adrenal glands ( < 0.01, FDR-adjusted = 0.05 and |FC| >2), respectively. Of these, four DEGs, namely , and , 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 ( < 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 (, and ) 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.
了解热应激生理学并确定可靠的生物标志物对于制定有效的管理和缓解策略至关重要。然而，对于动物耐热性的分子机制知之甚少。在一个实验模型中，将Sprague-Dawley大鼠置于22±1°C（对照组；CT）和42°C环境中30分钟（H30）、60分钟（H60）和120分钟（H120），对血液（CT和H120）、肝脏（CT、H30、H60和H120）以及肾上腺（CT、H30、H60和H120）进行RNA测序（RNA-Seq）分析。在血液（P<0.05且|倍数变化（FC）|>2）、肝脏（P<0.01，错误发现率（FDR）校正后P = 0.05且|FC|>2）和肾上腺（P<0.01，FDR校正后P = 0.05且|FC|>2）中分别显著鉴定出53个、1310个和1501个差异表达基因（DEG）。其中，在CT与H120比较中，三个组织共有四个DEG，即[此处原文缺失基因名称]。对血液（CT与H120）中鉴定出的DEG进行功能富集分析，发现12个生物学过程（BP）和25条代谢途径显著富集（FDR = 0.05）。在肝脏中，通过比较CT与H30、H60和H120，显著检测到133个BP和三条代谢途径。此外，肾上腺中237个BP显著富集（FDR = 0.05），在不同热应激组的大鼠中未检测到共享的代谢途径。在不同比较中，肝脏和肾上腺中分别有73个和91个共享DEG揭示了五种和四种表达模式（P<0.05）。其中，分别有69个和73个基因被提议作为调节大鼠热应激反应的候选基因。最后，结合牛的全基因组关联研究（GWAS）结果和人类的全表型关联研究（PheWAS）分析，五个基因（[此处原文缺失基因名称]）被认为与跨哺乳动物物种的热应激反应相关。本研究的数据集和结果将有助于更好地理解哺乳动物的热应激反应，并有助于通过育种开发减轻家畜热应激反应的有效方法。
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