The Human Early Maternal–Embryonic Interactome

Background: Single cell transcriptomics offers an avenue for predicting, with improved accuracy, the gene networks that are involved in establishment of first direct cell–cell interactions between blastocyst and maternal luminal epithelium. We hypothesised silico modelling maternal–embryonic interface may provide a causal model these interactions, leading to identification genes associated successful initiation implantation. Methods: Bulk single RNA-sequencing endometrial epithelium scRNAseq day 6 7 trophectoderm (TE) were used initial encounter uterine lining silico. In was performed using hypernetwork (HN) analysis mediating endometrial–TE wider epithelial transcriptome. A identifies co-ordinate expression many other derive higher order interaction likely be causally linked function. Potential TE non-ciliated cells, ciliated glandular cells examined. Results: Prominent activities include secretion, endocytosis, ion transport, adhesion, immune modulation. Three highly correlated clusters 25, 22 26 TE-interacting surface identified, each distinct properties. Genes both exhibit significant functional associations. Ciliated predicted bind via galectin–glycan interaction. Day embryonic–epithelial interactomes largely similar. The removal aneuploid TE-derived mRNA invoked only subtle differences. No gland is predicted. These differences validate segregation phenotypes. revealed change cycle phase, but phenotype individual donors also present. Conclusions: can identify show during menstrual interfaced predict pathways processes occurring embryo–epithelial mid-secretory phase. data on scale realistic dissection current ex vivo human implantation models. focus allow resolution bottleneck receptivity testing based tissue lysates, which confounded by noise from multiple diverse populations.