Effects Of Stress Mimicked By Corticosterone Administration On The Proliferation And Differentiation Of Intestinal Epithelial Cells In Broiler Chickens

Intestinal stem cells drive programmed renewal of the small intestinal epithelium,contributing to intestinal barrier function,absorption function,immune function and endocrine function.In this study,we aim to address the problem that stress damages the structural and functional integrity of the intestinal tract,models exogenous glucocorticoid exposure,explores the effects of stress on the proliferation and differentiation of broiler intestinal epithelial cells,reveals the mechanism of intestinal mucosal damage in stressed poultry mediated by intestinal stem cells and provides effective intervention targets for the regulation of intestinal health in poultry.A total of 252 male AA broilers at 28 days of age were selected and randomly divided into 3 groups of 6 replicates each,with 14 chickens in each replicate.One group is the control group,fed normally,the other group was fed 30 mg/kg of Corticosterone(CORT)in the diet;the third feeding pair(PF)was fed the same diet as the control group,and the daily feeding rate was the same as the previous day’s feeding rate of the CORT group.At the age of 36 days,two broiler chickens were taken from each replicate,blood was collected,slaughtered,and sampled.The results revealed that CORT exposure decreased jejunal villus height and Claudin-1 gene expression(P < 0.05)and increased blood lipopolysaccharide(LPS)content and diamine oxidase(DAO)activity(P < 0.05)in broiler chickens compared with the control group;Compared with the PF group,Broiler jejunal villus height was also reduced and blood LPS levels were increased in the CORT-treated group,suggesting increased intestinal permeability and impaired barrier function.Compared with the control group,CORT treatment significantly downregulated the m RNA expression of the intestinal stem cell marker genes Lgr5 and Hop X and the enteroendocrine cell marker genes CHGA and Paneth cell marker gene Lysozyme(P < 0.05)and increased the m RNA abundance of the Goblet cell marker gene MUC2(P < 0.05);compared with the PF group,the CORT-treated group m RNA expression of the intestinal stem cell gene HOPX and the enteroendocrine cell marker gene CHGA was also decreased in the CORT-treated group(P < 0.05),indicating a decrease in the number of intestinal stem cells,endocrine-type cells and Paneth cells,increase of Goblet cells.In addition,CORT upregulated the m RNA expression of Notch1(P < 0.05)and reduced the m RNA expression of Cyclin-D1,C-Myc and Axin2 in the Wnt/β-Catenin signaling pathway(P < 0.05),suggesting alterations in the regulatory pathways of intestinal stem cell proliferation and differentiation.The above results showed that CORT treatment(30 mg/kg for 8 d)reduced the number of broiler intestinal stem cells,endocrine-type cells and Paneth cells by down-regulating the expression of genes related to Wnt/β-Catenin signaling pathway and up-regulating the expression of Notch1 gene,induced the differentiation of intestinal stem cells to Goblet cells,which in turn inhibited the development of crypt chorion axis and disrupted the structural integrity of the intestine.