Immune regulation of conception and embryo implantation—all about quality control?

Medawar's hypotheses for explaining maternal immune tolerance of the semi-allogeneic fetus are now proven incorrect or insufficient. The mother's immune response is not passive, suppressed, indolent or physically constrained in pregnancy. Instead, her immune system is centrally engaged with all steps of the reproductive process from conception to embryo implantation and placental development. Emerging studies show that immune cells are positioned and equipped to sense antigens and other signals originating in seminal fluid, the embryo and placental trophoblast. The immune response appears competent to utilise this information to discriminate the reproductive fitness and compatibility of the male partner and the integrity and developmental competence of the conceptus tissue. Since the immune response is modulated by the individual's infectious, inflammatory, stress, nutritional and metabolic status, immune influence on progression or disruption of pregnancy may be further influenced by environmental stressors and resource availability. This opinion paper advances the view that the immune system operates in pregnancy to integrate these signals and to exert executive quality control to either accommodate or reject the conceptus. It is argued that ‘immune-mediated quality control’ would facilitate optimal female reproductive investment and maximise offspring fitness, and thereby explain the evolutionary advantage of maternal immune awareness of the conceptus tissue.