PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Maternal immunological adjustments to pregnancy and parturition in ruminants and possible implications for postpartum uterine health: Is there a prepartum-postpartum nexus?

Establishment of microbial infections in the reproductive tract can have negative consequences for reproductive function of the postpartum female. Most periparturient cows experience bacterial contamination of the uterus after parturition, but only a fraction of these develop subclinical or clinical disease. It is not well understood why one female resolves uterine infections after parturition while another develops disease. Perhaps those that develop metritis or endometritis are exposed to a greater bacterial load at parturition than those that successfully restore the uterus to a healthy condition. A second possibility is that females that develop bacterial disease have compromised immune function, either systemically or in the reproductive tract and associated lymph nodes. Here, the possibility is raised that maternal immunological adjustments to the presence of the allogeneic conceptus may predispose some females to metritis or endometritis. Several regulatory processes ensure that adaptive immune responses against paternal antigens on the conceptus are downregulated during pregnancy. Among these are immunosuppressive effects of progesterone, local accumulation of immune cells that can inhibit inflammation and T cell responses, including M2 macrophages and gamma delta T cells, and differentiation of regulatory T cells to inhibit alloreactive lymphocytes. Some immunological adjustments to the conceptus also make the uterus more susceptible to bacterial infection. For example, progesterone not only depresses skin graft rejection but also reduces uterine capacity to eliminate bacterial infections. Macrophages of M2 phenotype can inhibit inflammation and facilitate persistence of some microbial infections. At parturition, immune defenses in the uterus may be further weakened by loss of the luminal epithelium of the endometrium, which is part of the innate immune system, as well as by disappearance of intraepithelial gamma delta T cells that produce the antibacterial proteins granulysin and perforin. It is currently not known whether molecules and cells that inhibit immune responses during pregnancy persist after parturition but, if so, they could contribute to compromised immune function in the uterus. It is hypothesized that individual variation in immune adjustments to pregnancy and parturition and the reversal of these changes in the postpartum period are important determinants of susceptibility of the uterus to infection.