ABSTRACT
Viviparity is the hallmark of mammalian gestation, where progeny remains within the mother’s body throughout fetal development. Once recognized and accepted, the embryo receives nutrition and protection. Thus, immunological acceptance and tolerance are paramount to the successful interaction between the embryo graft and its maternal host. Initial immunological awareness must take place prior to implantation. The semipermeable zona pellucida forms rapidly postfertilization and protects the embryo until it reaches the endometrium. The zona is surrounded by maternal immune cells, and this unit transmits the message that fertilization has occurred. The main question is when and how the embryo-maternal communication initiates and creates maternal recognition of pregnancy. This is the main topic of this chapter. Further, we will focus on preimplantation factor (PIF), a peptide secreted by viable embryos which plays an essential role in pregnancy promoting embryo development, uterine priming, trophoblast invasion, and systemic immune regulation. This recognition starts prior to direct embryo-maternal contact in the uterus. Finally, data generated using nonpregnant models of autoimmune disorders and transplantation also provide important insight into PIF’s possible role in pregnancy.
In 1973, Beer and Billingham,1 while working on immunological recognition mechanisms in mammalian pregnancy, suggested that the maternal system is aware of the presence of the early embryo, and actively responds to it. This was surprising considering the differences in genetic makeup of the mother and fetus (semi-or total), and contrary to the prevailing opinion at that time, which considered that the trophoblast was hypoantigenic, protecting it from cellular immunity. The same authors also suggested that unique human leukocyte antigens (HLA) are presented to the maternal system, the responses to which play a role in establishing and maintaining pregnancy. A decade later, it was suggested2 that local, cell-based immunosuppressive and immunoprotective activity in the placenta was mediated by suppressor and other unknown cells. They further suggested that HLA sharing by parents leads to lack of maternal recognition and is therefore the basis for rejection, that is, miscarriage.
