Analysis of transcriptomic changes in bovine endometrial stromal cells treated with lipopolysaccharide

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold> Endometritis adversely affects the ability of cattle to reproduce, and significantly reduces milk production. Consequently, it has great influence on the economic value of dairy cows. The endometrium is mainly composed of epithelial and stromal cells and they produce the first immune response to invading pathogens. Epithelial cells are the first cellular barrier through which bacteria enter the uterine endometrium. However, most of the epithelial cells are disrupted and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. A loss of the protective epithelium allows bacteria or toxins to access the underlying stromal cells. The activation of Toll-like receptor（TLRs）on stromal cells induces increased production of cytokines and chemokines. Understanding the genome-wide characterization of the bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine stromal cells treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing (RNA-seq). <jats:bold>Results:</jats:bold> Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted <jats:italic>P</jats:italic>-value＜0.05 by DESeq. Gene ontology (GO) enrichment analysis revealed DEGs were most enriched in lymphocyte activation, interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in TNF signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway.<jats:bold>Conclusion:</jats:bold> The results of this study unraveled endometrial stromal cells transcriptome profile alterations in bovine affected by LPS which may have a significant effect on the eliminating or reducing inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.</jats:p>

Endometrial gene expression in response to lipopolysaccharide between estrous cycle phases and uterine horns in cattle

“…A greater response of IL-1a than IL-1b and IL-6 relative to controls was observed in LPS treated endometrial cells, suggesting IL-1a aids in upregulating the inflammatory response to LPS (Healy et al, 2014). The IL-17 signalling pathway was also identified as a major inflammatory pathway in LPS stimulation (Ding et al, 2020). The chemokine CCL3 is produced by immune cells, such as macrophages and dendritic cells, to upregulate an inflammatory response by recruiting additional immune cells for LPS clearance (Jing et al, 2003).…”

“…Differences in the expression of LPS binding pattern recognition receptor TLR4 and transcription factor NFkB1 were not detected in LPS treated explants. Previous studies have reported the ability of LPS to increase expression of TLR4, with other studies reporting minimal to no difference between control and LPS challenged tissues, potentially due to differences in LPS concentration and duration of exposure (Cronin et al, 2012;Swangchan-Uthai et al, 2012;Fu et al, 2013;Ding et al, 2020). The TLR4 receptors are present on endometrial tissue, including epithelial and stromal layers, and resident immune cells, such as macrophages, without LPS challenge in preparation for bacterial response (Herath et al, 2006;Dadarwal et al, 2017).…”

Analysis of Transcriptomic Changes in Bovine Endometrial Stromal Cells Treated With Lipopolysaccharide

“…endothelial cells and are involved in inflammation and immune functions (51). Each CAM has an inherent effect on the immune response process, such as VCAM-1, which promotes firm binding of T cells and induces transmigration (52,53).…”

“…This manuscript has been released as a preprint at https:// www.researchsquare.com/article/rs-7542/v3, Xuefen Ding, Haimiao Lv, Lixin Deng, Wenju Hu, Zhan Peng, Chenbo Yan, et al (53).…”