Transcriptome Changes of Human Embryo-Endometrial Cells Co-Culture <i>In Vitro</i> at Implantation Stages Revealed by Single-Cell RNA-Seq

Abstract

Background: In mammals, the blastocyst and maternal endometrium participate in the first physical and physiological interaction with each other to begin implantation. A bidirectional crosstalk is critical for normal implantation and then a successful pregnancy. While most studies use animal models or cell lines rather than human embryos, it is little knowledge but imperative to address this issue concerning human implantation. Results: Here, based on the established model and sequenced single-cell transcriptomes we previously published, we further explored the transcriptomic changes happened in endometrial cells and trophoblast cells after co-culture. These data showed that endometrial cells initiating extra-cellular matrix activity and trophoblast cells establishing invasion ability at the implantation stages. Compared with endometrium data in vivo and using the protein-protein interaction analysis, key genes were identified involving in the pathways, including FoxO signaling pathways and ErbB signaling pathways. Further analysis using CellphoneDB shed light on the underlying interactions between endometrium and embryos during embryo implantation. Conclusion: Our work revealed the synchronization signaling and pathways happening at the implantation stages involving the acquisition of receptivity in endometrial cells, the invasion ability in trophoblast cells and the interaction between each other. Funding Statement: This work was supported by grants from National Key R&D Program of China (2017YFC1001301, 2016YFC1000208) and the National Natural Science Foundation of China (81771651, 81873832). Declaration of Interests: The authors declare no competing interests.