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断奶前热应激会改变奶牛犊牛的肝脏转录组和DNA甲基化。

Preweaning heat stress alters liver transcriptome and DNA methylation in dairy calves.

作者信息

Laporta Jimena, Dado-Senn Bethany, Guadagnin Anne R, Liu Lihe, Peñagaricano Francisco

机构信息

Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706.

Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706.

出版信息

J Dairy Sci. 2025 Apr;108(4):4390-4402. doi: 10.3168/jds.2024-25975. Epub 2025 Jan 30.

DOI:10.3168/jds.2024-25975
PMID:39892602
Abstract

Prenatal hyperthermia has long-lasting effects on dairy calf metabolism, immunity, and productivity. Yet, the effects of postnatal heat stress on neonatal calves remain unclear. As such, this study aimed to investigate the impact of heat stress on the preweaning dairy calf liver gene expression and DNA methylation profiles. Holstein dairy calves were exposed to summer heat stress (daily average temperature-humidity index >78) for 42 d postnatally (i.e., birth to weaning) with access to active fan heat abatement (postnatal cooling, post-CL; calf-height air speed 2.05 m/s, n = 12) or not (postnatal heat stress, post-HS; calf-height air speed 0.15 m/s, n = 12). All thermoregulatory responses were lower in post-CL relative to post-HS calves throughout the experimental period (-12 bpm, -2.5°C, and -0.11°C for respiratory frequency, rectal temperature, and ear skin temperature, respectively). Liver tissue was harvested via biopsy (n = 6 male calves per treatment) at 42 d of age for RNA sequencing and reduced representation bisulfite sequencing. There were 73 differentially expressed genes (DEG), of which 31 were downregulated and 42 were upregulated in post-HS relative to post-CL treatments (false discovery rate cut-off, 20%). Ingenuity pathways analysis revealed that post-HS significantly affected 24 pathways and 60 transcription regulators, including pathway PI3K/AKT, and transcription regulators PPARGC1A, STAT5B, CREB, and XBP1. A total of 14,639 differentially methylated cytosines (DMC) were found across the entire bovine genome; these DMC mapped to 3,197 differentially methylated genes (DMG), with about 300 DMG with DMC located close to the transcription start site. These DMG, such as PKA, AMPK, MAPK, and STAT3, are closely related to metabolic signaling pathways. Overall, preweaning exposure of dairy calves to heat stress changes hepatic methylation profiles, which in turn may affect the expression of genes with critical roles in intracellular signaling and development, metabolic, and immune-related pathways. Providing mechanical cooling via fans to dairy calves in summer seems beneficial to promoting thermoregulation and liver cellular hemostasis.

摘要

产前高温对犊牛的代谢、免疫和生产性能具有长期影响。然而,产后热应激对新生犊牛的影响仍不清楚。因此,本研究旨在调查热应激对断奶前犊牛肝脏基因表达和DNA甲基化谱的影响。荷斯坦犊牛在出生后42天(即从出生到断奶)暴露于夏季热应激(日平均温湿度指数>78)环境中,一部分犊牛有主动风扇降温设备(产后降温组,post-CL;犊牛高度处风速2.05米/秒,n = 12),另一部分没有(产后热应激组,post-HS;犊牛高度处风速0.15米/秒,n = 12)。在整个实验期间,相对于post-HS组,post-CL组犊牛的所有体温调节反应均较低(呼吸频率、直肠温度和耳部皮肤温度分别降低-12次/分钟、-2.5°C和-0.11°C)。在42日龄时通过活检采集肝脏组织(每个处理6头雄性犊牛),用于RNA测序和简化代表性亚硫酸氢盐测序。共发现73个差异表达基因(DEG),与post-CL组相比,post-HS组中有31个基因下调,42个基因上调(错误发现率截止值为20%)。 Ingenuity通路分析显示,post-HS组显著影响24条通路和60个转录调节因子,包括PI3K/AKT通路以及转录调节因子PPARGC1A、STAT5B、CREB和XBP1。在整个牛基因组中总共发现了14,639个差异甲基化胞嘧啶(DMC);这些DMC定位到3,197个差异甲基化基因(DMG),其中约300个DMG的DMC位于转录起始位点附近。这些DMG,如PKA、AMPK、MAPK和STAT3,与代谢信号通路密切相关。总体而言,断奶前犊牛暴露于热应激会改变肝脏甲基化谱,进而可能影响在细胞内信号传导、发育、代谢和免疫相关通路中起关键作用的基因的表达。夏季为犊牛提供风扇机械降温似乎有利于促进体温调节和肝脏细胞稳态。

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