Bacterial infections of the endometrium after parturition commonly cause metritis and endometritis in dairy cattle, and these diseases are important because they compromise animal welfare and incur economic costs, as well as delaying or preventing conception. Here we highlight that uterine infections cause infertility, discuss which bacteria cause uterine disease, and review the evidence for mechanisms of inflammation and tissue damage in the endometrium. Bacteria cultured from the uterus of diseased animals include Escherichia coli, Trueperella pyogenes, and several anaerobic species, but their causative role in disease is challenged by the discovery of many other bacteria in the uterine disease microbiome. Irrespective of the species of bacteria, endometrial cell inflammatory responses to infection initially depend on innate immunity, with Toll-like receptors binding pathogen-associated molecular patterns, such as lipopolysaccharide and bacterial lipopeptides. In addition to tissue damage associated with parturition and inflammation, endometrial cell death is caused by a cholesterol-dependent cytolysin secreted by T. pyogenes, called pyolysin, which forms pores in plasma membranes of endometrial cells. However, endometrial cells surprisingly do not sense damage-associated molecular patterns, but a combination of infections followed by cell damage leads to release of the intracellular cytokine interleukin (IL)-1 alpha from endometrial cells, which then acts to scale inflammatory responses. To develop strategies to limit the impact of uterine disease on fertility, future work should focus on determining which bacteria and virulence factors cause endometritis, and understanding how the host response to infection is regulated in the endometrium.

In dairy cattle, uterine infections are not life threatening and often unavoidable; however, they reduce fertility and increase the production costs of properties. The aim of this study was to evaluate the incidence of subclinical endometritis from 32 to 70 days in milk (DIM) and its effects on the reproductive performance of crossbred dairy cows. Lactating cows (Holstein/Gir; n = 172), with no history of retained placenta, without clinical signs of uterine infection were used. The body condition score (BCS) was evaluated on a scale from 1 to 5. Ultrasound examination was performed to evaluate uterine lining and ovarian activity, while vaginal mucus was analyzed by gloved hand. The diagnosis of subclinical endometritis was performed by endometrial cytobrush technique. The samples were collected, stained, and examined microscopically; positive cases for subclinical endometritis were considered with the presence of ≥5 % of neutrophils. Later, the cows were submitted to conventional artificial insemination or timed artificial insemination. The incidence of subclinical endometritis in the herd was 26 %, and this was not affected by the season of calving, presence of corpus luteum, DIM, and parity. Cows with a BCS ≤2.50 had a higher incidence of subclinical endometritis. The conception rate to first insemination and pregnancy rate at 150 days postpartum were not influenced by the presence of subclinical endometritis in crossbred dairy cows.

Bovine herpesvirus-4 (BoHV-4) and bovine viral diarrhea virus (BVDV) infect the uterus of cattle, often resulting in reduced fertility, or abortion of the fetus, respectively. Here, exposure of primary bovine endometrial cells to BoHV-4 or BVDV modulated the production of inflammatory mediators. Viral pathogen-associated molecular patterns (PAMPs) are detected via pattern-recognition receptors (PRRs). However, the relative contribution of specific PRRs to innate immunity, during viral infection of the uterus, is unclear. Endometrial epithelial and stromal cells constitutively express the PRR Toll-like receptor (TLR)-3, but, the status of retinoic acid-inducible gene I (RIG-I), a sensor of cytosolic nucleic acids, is unknown. Primary endometrial epithelial and stromal cells had low expression of RIG-I, which was increased in stromal cells after 12 h transfection with the TLR3 ligand Poly(I:C), a synthetic analog of double-stranded RNA. Furthermore, short interfering RNA targeting TLR3, or interferon (IFN) regulatory transcription factor 3, an inducer of type I IFN transcription, reduced Poly(I:C)-induced RIG-I protein expression and reduced inflammatory mediator secretion from stromal cells. We conclude that antiviral defense of endometrial stromal cells requires coordinated recognition of PAMPs, initially via TLR3 and later via inducible RIG-I.