Uterine infection alters bovine endometrium, oviduct and granulosa transcriptome three months later

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. Overall design: The present study aimed to explore whether uterine infection with bacteria that cause endometritis leads to long-term changes in the reproductive tract. Specifically, 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. To test this hypothesis, we exploited a model of clinical endometritis in virgin Holstein heifers, which allowed us to avoid the confounding effects of periparturient problems, metabolic stress and lactation (Piersanti et al. 2019b). We infused animals intrauterine with control vehicle or with E. coli and T. pyogenes to induce endometritis, and collected endometrium, oviduct and granulosa cells three months later. We then compared the transcriptomes of each of these tissues between bacteria-infused and control animals using RNA-sequencing (RNAseq) and pathway analysis.