Dynamic of intrauterine crosstalk promotes embryo implantation in early pregnancy

The success of early pregnancy depends largely on the successful implantation of the embryo. Dynamic crosstalk between embryo and mother plays a crucial role in this process, but our understanding is still limited. Here, using the pig as a model, we first comprehensively profile the single-cell transcriptome of early free embryos and corresponding maternal endometrium, identifying embryonic and matched endometrial cells with heterogeneity. We developed a novel tool, ExtraCellTalk, to predict crosstalk between the early embryo and the maternal uterus using uterine luminal proteins as bridges, generating an overall dynamic map of maternal-fetal crosstalk. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 targets the STRA6 receptor on stromal cells in the endometrium, thereby interacting with endothelial and perivascular cells to regulate their interconversion to promote endometrial remodeling. These maternal-fetal crosstalks and corresponding endometrial changes that we uncovered are essential for subsequent embryo implantation and are the basis for further studies to improve embryo implantation. Overall design: Pig embryos and endometrium on days 9 and 12 of pregnancy.