热应激引起的肠道炎症是限制肉鸡健康生长的重要因素。本研究旨在评估鸡胚胎热处理（在胚胎期16-18天每天进行3小时，温度为39.5℃，相对湿度为65%）对肉鸡产后热应激下肠道炎症的影响，并调查瞬时受体电位V4（TRPV4）是否在这一过程中发挥作用。我们的结果表明，经历过胚胎热处理的肉鸡能延迟产后热应激期间肛温的上升（P<0.05），并具有更好的生产性能（P<0.05）、肠道形态学参数（P<0.05）以及更高的紧密连接相关基因表达（P<0.05）。经过胚胎热处理的肉鸡在产后热应激期间，血清内毒素（LPS）含量增加、核因子-κB（NF-κB）信号通路的激活以及空肠内前炎症细胞因子白细胞介素（IL）-1β、IL-6和肿瘤坏死因子α（TNF-α）表达的增加均得到缓解（P<0.05）。产后热应激诱导空肠TRPV4的mRNA和蛋白质表达增加（P<0.05），但经过胚胎热处理的肉鸡没有发生此现象（P>0.05）。TRPV4抑制剂可降低LPS诱导的Ca2+流入，抑制NF-κB信号通路的激活和下游炎性因子表达（P<0.05）。经过胚胎热处理的肉鸡的空肠DNMT表达增加（P<0.05）。检测了TRPV4启动子区域的DNA甲基化水平，结果表明，经过胚胎热处理可提高TRPV4启动子区域的DNA甲基化水平（P<0.05）。结论：鸡胚胎热处理可缓解产后热应激下肉鸡空肠炎症。这可能是由于循环内毒素减少或TRPV4启动子区域DNA甲基化水平上升引发的，后者可以抑制TRPV4表达，从而减少Ca2+流入，最终通过影响NF-κB信号通路缓解炎症。本研究旨在了解产前热处理缓解产后热应激不良影响的机制，并揭示表观遗传学在其中的重要作用。版权所有©2023年作者。由Elsevier Inc.出版。保留所有权利。

Intestinal inflammation induced by heat stress is an important factor restricting the healthy growth of broilers. The aim of this study was to evaluate the effect of chicken embryo thermal manipulation (39.5 ℃ and 65 % RH for 3 h daily during 16-18 th embryonic age) on intestinal inflammation in broilers under postnatal heat stress and to investigate whether transient receptor potential V4 (TRPV4) plays a role in this process. Our results suggest that broilers with embryo thermal manipulation experience could delay the rising of rectal temperature during postnatal heat stress (P < 0.05), and had better production performance (P < 0.05), intestinal morphological parameters (P < 0.05) and higher expression of tight junction related genes (P < 0.05). The increased serum lipopolysaccharide (LPS) content, activation of nuclear factor-kappa B (NF-κB) signaling pathway and the increased expression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α) in jejunum during postnatal heat stress were alleviated by embryo thermal manipulation (P < 0.05). Postnatal heat stress induced an increase in mRNA and protein expression of TRPV4 in jejunum (P < 0.05), but had no effect on broilers which experienced embryo thermal manipulation (P > 0.05). Inhibition of TRPV4 reduced LPS-induced Ca2+ influx and restrained the activation of NF-κB signaling pathway and the expression of downstream pro-inflammatory cytokines (P < 0.05). The expression of DNA methyltransferase (DNMT) in the jejunum of broilers exposed to postnatal heat stress was increased by embryo thermal manipulation (P < 0.05). The DNA methylation level of TRPV4 promoter region was detected, and the results showed that embryo thermal manipulation increased the DNA methylation level of TRPV4 promoter region (P < 0.05). In conclusion, Chicken embryo thermal manipulation can alleviate jejunal inflammation in broilers under postnatal heat stress. This may be due to the decreased circulating LPS or the increased DNA methylation level in the promoter region of TRPV4, which inhibits TRPV4 expression, thereby reducing Ca2+ influx, and finally alleviating inflammation by affecting NF-κB signaling pathway. The work is an attempt to understand the mechanism involved in alleviation of adverse effects of heat stress during postnatal life through prenatal thermal manipulation and to reveal the important role of epigenetics.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.