Induced Uterine Infection Alters Bovine Endometrial Function and Embryonic Competence

Uterine diseases in dairy cattle are associated with reduced fertility, but the specific mechanisms of disease-mediated subfertility are not known. We hypothesized that intrauterine infusion of Escherichia coli and Trueperella pyogenes would alter the endometrial transcriptome and compromise oocyte developmental competence after disease resolution. Non-lactating Holstein cows received an intrauterine infusion of either sterile phosphate-buffered saline (n = 29) or pathogenic E. coli and T. pyogenes (n = 32) on day 3 of the estrous cycle to induce acute endometrial inflammation. Oocytes of antral follicles were collected by ovum pick-up following estrous synchronization 23 days after intrauterine infusion and underwent in vitro embryo production. Endometrial samples were collected on day 16 of the estrous cycle via cytobrush 41 days after infusion and analyzed by RNA sequencing. Bacterial infusion had no effect on oocyte development to the blastocyst stage, but increased blastocyst expression of CDK7, CHSY1, and LSM4 and tended to reduce the molecular signature of embryo competence for survival. Bacterial infusion altered the expression of 203 genes in the endometrium 41 days after infusion, increasing expression of GSTA3, PVALB, JAKMIP2, FOLH1B, and TCF23, and decreasing expression of MYMK, LOC104974498, CDRT1, KIAA0408, and SLC45A2. Differentially expressed genes were annotated to 54 canonical pathways, with glutathione-mediated detoxification being the top predicted pathway activated following bacterial infusion. Collectively, this work demonstrates that bacterial infections can have lasting effects on the uterus and potentially reduce the molecular competence of oocytes, providing a link to the long-term subfertility of cows after uterine disease.