Embryo-maternal signalling: how the embryo starts talking to its mother to accomplish implantation

Abstract

The process of implantation and trophoblast invasion is currently considered as the most limiting factor for the establishment of pregnancy. Molecular interactions at the embryo–maternal interface during the time of adhesion and subsequent invasion are crucial to the process of embryonic implantation. Both partners, the mother as well as the embryo, play equal roles in the embryo–maternal dialogue, the embryonic part being the main topic in this study. Investigations of the proteins in the extra-embryonic matrices (i.e. zona pellucida) indicate that the embryo participates intensively in this early embryo–maternal signalling. One unique feature during implantation process of primate embryos is the release of chorionic gonadotrophin, which seems to influence endometrial activity by two different mechanisms: (i) luteotrophic activity with increasing progesterone release and (ii) a direct action on the endometrium. Furthermore, embryonic interleukin-1β may be involved in embryo–maternal signalling. Other significant signals in this interaction are most likely leukaemia inhibitory factor (LIF) and colony-stimulating factor (CSF), which stimulate matrix metalloproteinase (MMP)/insulin-like growth factor binding protein-1 (IGFBP-1) activity and the insulin-like growth factor (IGF) system, which is modulated by embryonic IGFBP-3. Similar significances are discussed for uteroglobin and haptoglobin. Finally, the phenomenon of maternal immunological tolerance, triggered by the presence of the early embryo, is fundamental to the understanding of implantation and trophoblast invasion. A tightly regulated balance between activated and inactivated T cells at the implantation site may control the beginning of adequate trophoblast invasion and also limit this invasion to a tolerable extent for the maternal system, consequently ensuring a biologically healthy haemo-chorial placenta.