Immune balance at the foeto-maternal interface as the fulcrum of reproductive success

Abstract

Viviparity has many evolutionary advantages but brings with it the problem of the semi-allogeneic foetus having to coexist with the mother for the duration of pregnancy. In species with haemochorial placentation this problem is particularly evident as foetal trophoblast cells are extensively intermingled with maternal tissue and are directly exposed to maternal blood. Fascinating adaptations on both the foetal and maternal side have allowed for this interaction to be re-directed away from an immune rejection response not only towards immunotolerance, but in fact towards actively supporting reproductive success. Recent data have shown that some of these remarkable adaptations are conserved between mice and humans. Thus, a subset of trophoblast cells that is directly exposed to the maternal uterine environment shares the feature of expressing an unusual antigen repertoire on their surface. Paternal antigens can be recognized by maternal immune cells, in particular uterine natural killer cells that express cognate receptors, to regulate the extensive remodelling events that take place at the implantation site. Detailed genetic dissection experiments in the mouse have further demonstrated the direct impact of antigenic dissimilarity on foetal growth. With the availability of inbred strains, in vitro culture systems of trophoblast stem cells, and in-depth genetic, genomic and epigenomic data the mouse will be a valuable model system to study the intricate immune crosstalk at the foeto-maternal boundary. These insights will pave the way towards unravelling the mutual and synergistic interactions between trophoblast and its surrounding maternal environment, and in doing so help understand pregnancy pathologies.