Intrauterine infusion of pathogenic bacteria persistently the transcriptome of oocytes.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA593028 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10574574_1.fastq.gz | Fastqsanger.gz | |||
| SRR10574574_2.fastq.gz | Fastqsanger.gz | |||
| SRR10574575_1.fastq.gz | Fastqsanger.gz | |||
| SRR10574575_2.fastq.gz | Fastqsanger.gz | |||
| SRR10574576_1.fastq.gz | Fastqsanger.gz |
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Project description:To better understand the impact of infection on oocyte quality we employed global transcriptomics of oocytes collected from heifers after receiving intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes. We hypothesized that oocyte transcriptome would be altered in response to intrauterine infection. A total of 452 differentially expressed genes were identified in oocytes collected from heifers 4 days after bacteria infusion compared to vehicle infusion, while 539 differentially expressed genes were identified in oocytes collected from heifers 60 days after bacteria infusion. Only 42 genes were differentially expressed in bacteria infused heifers at both day 4 and day 60. Interferon, HMGB1, ILK, IL-6 and TGF-beta signaling pathways were downregulated in oocytes collected at day 4 from bacteria infused heifers, while interferon, ILK and IL-6 signaling were upregulated in oocytes collected at day 60 from bacteria infused heifers. These data suggest that bacterial infusion alters the oocyte transcriptome differently at day 4 and day 60, suggesting different follicle stages are susceptible to damage. Characterizing the long-term impacts of uterine infection on oocyte transcriptome aids in our understanding of how infection causes infertility in dairy cattle.
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Project description:Here we tested the hypothesis that intrauterine infusion of pathogenic bacteria leads to changes in the transcriptome of the reproductive tract in dairy cattle three months later. We used virgin Holstein heifers to avoid the confounding effects of periparturient problems, metabolic stress and lactation. Animals were infused intrauterine with endometrial pathogenic bacteria Escherichia coli and Trueperella pyogenes to induce clinical endometritis (n = 4) and compared with control animals (n = 6). Three months after infusion, the caruncular and intercaruncular endometrium, isthmus and ampulla of the oviduct, and granulosa cells from dominant ovarian follicles were profiled by RNA-sequencing. Compared with control, bacterial infusion altered the transcriptome of all the tissues. Most differentially expressed genes were tissue-specific, with 109 differentially expressed genes unique to the caruncular endometrium, 57 in the intercaruncular endometrium, 65 in the isthmus, 298 in the ampulla, and 83 in granulosa cells. Surprisingly, despite infusing the bacteria into the uterus, the granulosa cells had more predicted upstream regulators of differentially expressed genes than all the other tissues combined. In conclusion, there was evidence of long-term changes to the transcriptome of the endometrium, oviduct and even the granulosa cells after intrauterine infusion of pathogenic bacteria, which implies that all these tissues contribute to the infertility that persists after endometritis.
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Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.
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