I-34: Interactorme of Human Embryo Implan Implantation:Pathways,Networks

Background: A prerequisite for successful embryo implantation is adequate preparation of receptive endometrium and the establishment and maintenance of a viable embryo. The success of implantation further relies upon a two-way dialogue between the embryo and uterus. However, molecular bases of these preimplantation and implantation processes in humans are not well known. Materials and Methods: We performed genome expression analyses of human embryos (n = 128) and human endometria (n = 8). We integrated these data with proteinprotein interactions in order to identify molecular networks within the endometrium and the embryo, and potential embryo-endometrium interactions at the time of implantation. For that we applied a novel network profiling algorithm HyperModules, which combines topological module identification and functional enrichment analysis. Results: We found a major wave of transcriptional downregulation in preimplantation embryos. In receptive-stage endometrium, several genes and signalling pathways were identified, including JAK-STAT signalling and inflammatory pathways. The main curated embryo-endometrium interaction network highlighted the importance of cell adhesion molecules in the implantation process. We also identified cytokine-cytokine receptor interactions involved in implantation, where osteopontin, LIF and LEP pathways were intertwining. Further, we identified a number of novel players in human embryo-endometrium interactions, such as APOD, EDN1, FGF7, GAST, KREMEN1, NRP1, SERPINA3, VCAN, and others. Conclusion: Our findings provide a fundamental resource for better understanding of the genetic network that leads to successful embryo implantation. We demonstrate the first systems biology approach into the complex molecular network of the implantation process in humans. Keywords: Implantation, Embryo-Endometrium Interactions, Receptive Endometrium