BREEDING INDUCED ENDOMETRITIS IN THE MARE: THE LOCAL INNATE IMMUNE RESPONSE

Uterine inflammation after breeding is considered necessary for the clearance of excess semen and debris from the uterus. A subpopulation of mares fails to clear the inflammation in a timely fashion, and develops a persistent breeding induced endometritis (PBIE). Experiments were preformed to evaluate correlations of PBIE to endometrial quality and age. Mares of advanced age and poor endometrial quality had a higher incidence of PBIE. In addition, mares fluctuated in susceptibility to PBIE from one season to the next. The uterine inflammatory gene expression in susceptible and resistant mares within the first 24 hours after breeding was investigated. The peak endometrial cytokine gene expression occurred 6 hours after insemination, and susceptible mares were found to have a reduced response of the inflammatory modulating cytokines during this time. Intrauterine accumulation of the inflammatory byproduct nitric oxide (NO) was investigated in resistant and susceptible mares within the first 24 hours after breeding. Susceptible mares had an increase in NO accumulation over time, whereas NO accumulation in resistant mares remained relatively constant. The effects of immunomodulators on uterine inflammatory response and nitric oxide accumulation in susceptible mares was investigated. Immunomodulators decreased expression of the pro-inflammatory cytokine interleukin-1β and nitric oxide accumulation. In conclusion, endometrial quality and age are indicators of susceptibility to PBIE, and susceptibly can change from year to year. Six hours after breeding is a critical time for the development of PBIE, and susceptible and resistant mares have differential endometrial inflammatory gene expression, with susceptible mares appearing to have a defect in the inflammatory modulating immune response. Finally, treatment with immune modulators alters the IL1β gene expression and intrauterine nitric oxide accumulation, which may help to explain how they act to reduce inflammation during PBIE