Regulation of embryonic implantation.

The preimplantation embryo produces several factors during its development to signal its presence to the maternal organism. This paper will focus on the role of two distinctive cytokine and growth factor systems (interleukin-1 (IL-1) system and the vascular endothelial growth factor (VEGF) system) during early embryonic development and implantation. IL-1 receptor is expressed in the endometrium of various species and antagonising the biological effects of IL-1 leads to implantation failure in mice. We could show that this is due to an endometrial, not an embryonic effect. Furthermore, we could detect the expression of all components of the IL-1 system in preimplantation embryos from mice and humans. We could show a possible influence of IL-1 on other systems involved in embryonic implantation, including invasion (MMPs/TIMPs) and angiogenesis (VEGF), therefore suggesting a role of this cytokine family during early embryonic development. Immediately after contact to the endometrium, the embryo must induce angiogenesis to ensure its survival, VEGF is a potent angiogenetic growth factor. We have shown a cyclic regulation of the soluble VEGF-receptor, sflt, in human endometrium and have detected the expression of the transmembraneous VEGF-receptors, Flt-1 and kinase insert domain containing receptor (KDR) throughout the menstrual cycle. Furthermore, we have shown that the VEGF gene is one of the earliest genes activated during human preimplantation embryo development, giving rise to the assumption that VEGF is crucial for embryonic development.