Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows
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ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE40312 | GEO | 2012/08/25
SECONDARY ACCESSION(S): PRJNA173688
REPOSITORIES: GEO
Similar Datasets
Project description:All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of endometrial inflammation showed a great degree of inflammation 15 days postpartum (DPP) which significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes elevated at both time points. Novel candidate genes of inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR). Endometrial biopsies were collected as part of a previous study 15 and 30 days postpartum (DPP) from 13 mixed breed beef multiparous cows. The endometrial transcriptomic profiles from endometrial biopsies were assessed by mRNA-Seq (n=3) and candidate gene expression was measured by qRT-PCR (n=5) comparing 15 DPP to 30 DPP samples. Reads were mapped to the bovine genome with TopHat, Htseq-count summarized the number of aligned reads per exon and EdgeR normalized the data and returned significantly differentially expressed genes. GoSeq identified KEGG pathways enriched by significantly differentially expressed genes elevated at both time points.
2012-08-25 | E-GEOD-40312 | biostudies-arrayexpress
Project description:The regulation of endometrial inflammation has important consequences for the resumption of bovine fertility post-partum. All cows experience bacterial influx into the uterus after calving; however a significant proportion fail to clear infection leading to the development of cytological endometritis (CE) and compromised fertility. We hypothesised that early immunological changes could not only act as potential prognostic biomarkers for the subsequent development of disease but also shed light on the pathogenesis of endometritis in the post-partum dairy cow. Here, next-generation sequencing from endometrial biopsies taken at 7 days post-partum (DPP) identified significant expression of inflammatory genes in all cows. Despite the common inflammatory profile and enrichment of the Toll-like receptor, NF?B and TNF signalling pathways, 73 genes and 31 miRNAs differentiated between healthy cows (HC, n=9) and cows which subsequently developed CE at 7 DPP (n=6, FDR<0.1). In healthy cows, 4197 differentially expressed genes between 7 and 21 DPP whereas only 31 genes were differentially expressed in samples from cows with CE. At 21 DPP, a further 1167 genes were differentially expressed between HC cows and cows diagnosed with CE (FDR<0.1). These changes in host gene expression reflected culture-independent microbiological analysis which showed significant differences in uterine bacterial profiles between groups. Inflammatory activity was not confined to the uterus; decreased circulating granulocytes and increased Acute Phase Protein (SAA and HP) plasma expression levels were detected at 7 DPP in cows that developed CE. In conclusion, our data suggests that the major inflammatory cascade activated early post-partum is resolved thereby restoring homeostasis in healthy cows by 21 DPP, but this transition fails to occur in cows which develop CE. Despite a common inflammatory profile, differential expression of specific immune genes may identify cows at risk of prolonged inflammation and the development of CE post-partum. Sixteen Holstein Friesian cows, of mixed parity, within the same university dairy herd were sampled 7 and 21 days postpartum (DPP) in the morning after milking, over an eight week period.
2015-08-01 | E-GEOD-66825 | biostudies-arrayexpress
Project description:The regulation of endometrial inflammation has important consequences for the resumption of bovine fertility post-partum. All cows experience bacterial influx into the uterus after calving; however a significant proportion fail to clear infection leading to the development of cytological endometritis (CE) and compromised fertility. We hypothesised that early immunological changes could not only act as potential prognostic biomarkers for the subsequent development of disease but also shed light on the pathogenesis of endometritis in the post-partum dairy cow. Here, next-generation sequencing from endometrial biopsies taken at 7 days post-partum (DPP) identified significant expression of inflammatory genes in all cows. Despite the common inflammatory profile and enrichment of the Toll-like receptor, NFκB and TNF signalling pathways, 73 genes and 31 miRNAs differentiated between healthy cows (HC, n=9) and cows which subsequently developed CE at 7 DPP (n=6, FDR<0.1). In healthy cows, 4197 differentially expressed genes between 7 and 21 DPP whereas only 31 genes were differentially expressed in samples from cows with CE. At 21 DPP, a further 1167 genes were differentially expressed between HC cows and cows diagnosed with CE (FDR<0.1). These changes in host gene expression reflected culture-independent microbiological analysis which showed significant differences in uterine bacterial profiles between groups. Inflammatory activity was not confined to the uterus; decreased circulating granulocytes and increased Acute Phase Protein (SAA and HP) plasma expression levels were detected at 7 DPP in cows that developed CE. In conclusion, our data suggests that the major inflammatory cascade activated early post-partum is resolved thereby restoring homeostasis in healthy cows by 21 DPP, but this transition fails to occur in cows which develop CE. Despite a common inflammatory profile, differential expression of specific immune genes may identify cows at risk of prolonged inflammation and the development of CE post-partum. Sixteen Holstein Friesian cows, of mixed parity, within the same university dairy herd were sampled 7 and 21 days postpartum (DPP) in the morning after milking, over an eight week period.
2015-08-01 | E-GEOD-66826 | biostudies-arrayexpress
Project description:Background: Physiological inflammation of the uterus postpartum is essential for the reparative processes of involution after calving. In the majority of cows, this inflammation is resolved and homeostasis is restored. However, in a significant subset, inflammation persists and contributes to tissue damage, pathology and subfertility. Transcriptomic differences of immune genes between cattle that resolve inflammation and those that develop uterine disease have been detected as early as 7 days postpartum (DPP) suggesting that the host immune response plays an important role in disease outcome. Results: Here, we extensively characterise the immune response at the transcriptomic level in endometrial epithelial cells from post-partum dairy cows phenotyped for both clinical and sub-clinical forms of uterine disease. We address the hypothesis that excessive expression of endometrial inflammatory molecules contributes to development of endometritis. Classification of cattle (n=112) as healthy or with uterine disease (purulent vaginal discharge; PVD and cytological endometritis; CYTO) was based on vaginal mucus score and >18% polymorphonuclear cell infiltrate into the endometrium at 21 DPP. RNA-seq analysis of endometrial epithelial cells collected using cytobrushes identified differential expression of 294 genes (FDR <0.05) between cows that subsequently resolved inflammation (n=10) and those that developed disease (n=20). Pathway over-representation analysis of differentially expressed genes (DEG) identified significant changes in immune-related pathways, including the NOD-like receptor signalling pathway, cytokine-cytokine receptor interaction pathway and the Toll-like receptor signalling pathway which were up-regulated in cattle that subsequently developed disease. The majority of the DEG were upregulated in cows that developed PVD, and included all genes upregulated in CYTO cows, suggesting a core inflammatory gene signature early post-partum contributes to the onset of uterine disease. This inflammatory signature was validated by qPCR in an independent group of cows (n=56) and included upregulation of pro-inflammatory genes (including TLR2, TLR4, NLRP3, IL1A, IL1B, IL8, and S100A8) at day 7 postpartum in cows that failed to resolve inflammation. Conclusions: Despite a large amount of inter-animal heterogeneity, these results suggest that excessive activation and inappropriate regulation of the inflammatory response early postpartum is a key feature of the subsequent development of uterine disease. Keywords: Endometritis, Inflammation, Transcriptome, Next generation sequencing, Dairy cattle, Uterine involution, Immune response
2019-04-01 | GSE125964 | GEO
Project description:This study was done to identify endometrial DNA methylation marks that can be associated with pregnancy outcomes in postpartum cows at the time of breeding. Results showed that postpartum cows that could become pregnant could be distinguishable based on their endometrial DNA methylation patterns at the time of breeding.
2023-12-25 | GSE248185 | GEO
Project description:The regulation of endometrial inflammation has important consequences for the resumption of bovine fertility post-partum. All cows experience bacterial influx into the uterus after calving; however a significant proportion fail to clear infection leading to the development of cytological endometritis (CE) and compromised fertility. We hypothesised that early immunological changes could not only act as potential prognostic biomarkers for the subsequent development of disease but also shed light on the pathogenesis of endometritis in the post-partum dairy cow. Here, next-generation sequencing from endometrial biopsies taken at 7 days post-partum (DPP) identified significant expression of inflammatory genes in all cows. Despite the common inflammatory profile and enrichment of the Toll-like receptor, NFκB and TNF signalling pathways, 73 genes and 31 miRNAs differentiated between healthy cows (HC, n=9) and cows which subsequently developed CE at 7 DPP (n=6, FDR<0.1). In healthy cows, 4197 differentially expressed genes between 7 and 21 DPP whereas only 31 genes were differentially expressed in samples from cows with CE. At 21 DPP, a further 1167 genes were differentially expressed between HC cows and cows diagnosed with CE (FDR<0.1). These changes in host gene expression reflected culture-independent microbiological analysis which showed significant differences in uterine bacterial profiles between groups. Inflammatory activity was not confined to the uterus; decreased circulating granulocytes and increased Acute Phase Protein (SAA and HP) plasma expression levels were detected at 7 DPP in cows that developed CE. In conclusion, our data suggests that the major inflammatory cascade activated early post-partum is resolved thereby restoring homeostasis in healthy cows by 21 DPP, but this transition fails to occur in cows which develop CE. Despite a common inflammatory profile, differential expression of specific immune genes may identify cows at risk of prolonged inflammation and the development of CE post-partum.
2015-08-01 | GSE66826 | GEO
Project description:The regulation of endometrial inflammation has important consequences for the resumption of bovine fertility post-partum. All cows experience bacterial influx into the uterus after calving; however a significant proportion fail to clear infection leading to the development of cytological endometritis (CE) and compromised fertility. We hypothesised that early immunological changes could not only act as potential prognostic biomarkers for the subsequent development of disease but also shed light on the pathogenesis of endometritis in the post-partum dairy cow. Here, next-generation sequencing from endometrial biopsies taken at 7 days post-partum (DPP) identified significant expression of inflammatory genes in all cows. Despite the common inflammatory profile and enrichment of the Toll-like receptor, NFκB and TNF signalling pathways, 73 genes and 31 miRNAs differentiated between healthy cows (HC, n=9) and cows which subsequently developed CE at 7 DPP (n=6, FDR<0.1). In healthy cows, 4197 differentially expressed genes between 7 and 21 DPP whereas only 31 genes were differentially expressed in samples from cows with CE. At 21 DPP, a further 1167 genes were differentially expressed between HC cows and cows diagnosed with CE (FDR<0.1). These changes in host gene expression reflected culture-independent microbiological analysis which showed significant differences in uterine bacterial profiles between groups. Inflammatory activity was not confined to the uterus; decreased circulating granulocytes and increased Acute Phase Protein (SAA and HP) plasma expression levels were detected at 7 DPP in cows that developed CE. In conclusion, our data suggests that the major inflammatory cascade activated early post-partum is resolved thereby restoring homeostasis in healthy cows by 21 DPP, but this transition fails to occur in cows which develop CE. Despite a common inflammatory profile, differential expression of specific immune genes may identify cows at risk of prolonged inflammation and the development of CE post-partum.
2015-08-01 | GSE66825 | GEO
Project description:In postpartum dairy cows, subclinical endometritis (SCE) is characterized by persistent endometrial inflammation, which exerts profound detrimental effects on subsequent reproductive performance. So far, transcriptomic studies related to this condition were either based on biopsy-derived whole endometrium tissue or endometrial swab/cytobrush samples, thus neglecting cell type-specific variations in gene expression. This study tested the hypothesis that different endometrial health statuses are associated with distinct transcription profiles of endometrial stromal, glandular and luminal epithelial cells. In conclusion, this study evidences that endometrial inflammation recovery or persistence is associated with gene expression patterns involved in immune function, tissue remodelling, and uterine receptivity in a cell type-specific manner. Identifying these signatures may prove instrumental to developing novel diagnostic and therapeutic targets, either to prevent persistence or speed recovery from endometrial inflammation, thus restoring the fertility of postpartum dairy cows.
2022-04-20 | GSE192545 | GEO
Project description:Cattle with subclinical endometritis (SCE) are sub-fertile, but there is no predictive or diagnosis tool for subclinical uterine disease. The hypothesis for this study was that endometrial inflammation is reflected in peripheral blood leucocytes gene expression. Transcriptome patterns in healthy cows and in cows with SCE at 45-55 days postpartum were evaluated using circulating white blood cells and endometrial biopsies samples collected from the same animals. Bioinformatics analyses of microarray-based transcriptional data identified gene profiles associated with distinct biological functions in circulating white blood cells and endometrium. In circulating white blood cells SCE promote a pro-inflammatory environment related to the activation of inflammation, whereas in the endometrium functions also related to tissue remodeling. Nineteen differentially expressed genes were altered both in circulating white blood cells and in the endometrium of SCE cows compared with healthy cows. Among these genes, transcript abundance of immune factors C3, C2, LTF, PF4 and TRAPPC13 were up-regulated in SCE cows at 45-55 days postpartum. Moreover, the mRNA expression of C3, CXCL8, LTF, TLR2 and TRAPPC13 was temporally regulated during the postpartum period in circulating white blood cells from healthy cows compared with SCE cows. This observation might indicate an advantageous activation of the immune system in healthy animals. The transcript abundance of these genes might also be used as an indicator for subsequent postpartum uterine health.
2019-08-20 | GSE115667 | GEO
Project description:To clarify the regenerative mechanism of endometrium after parturition in cows, mRNA expression profiles in bovine endometrium were investigated during postpartum period. after PVP-I treatment in cows. The differentially expressed genes in the endometrium between postpartum days 49-52 and days 99-101 were 23 genes, and they were much lower than those before postpartum days 49-52. This result suggests that endometrial regeneration after parturition is completely accomplished until postpartum days 49-52.
2021-01-16 | GSE164924 | GEO