Specific trophoblast transcripts transferred by extracellular vesicles affect gene expression in endometrial epithelial cells and may have a role in embryo-maternal crosstalk

Es-Haghi, Masoumeh; Godakumara, Kasun; H�ling, Annika; L�ttekivi, Freddy; Lavrits, Arina; Viil, Janeli; Andronowska, Aneta; Nafee, Tamer; James, Victoria; Jaakma, �lle; Salumets, Andres; Fazeli, Alireza

Abstract

© 2019 The Author(s). Background: Successful establishment of pregnancy hinges on appropriate communication between the embryo and the uterus prior to implantation, but the nature of this communication remains poorly understood. Here, we tested the hypothesis that the endometrium is receptive to embryo-derived signals in the form of RNA. Methods: We have utilized a non-contact co culture system to simulate the conditions of pre implantation environment of the uterus. We bioorthogonally tagged embryonic RNA and tracked the transferred transcripts to endometrium. Transferred transcripts were separated from endometrial transcripts and sequenced. Changes in endometrial transcripts were quantified using quantitative PCR. Results: We show that three specific transcripts are transferred to endometrial cells. We subsequently demonstrate a role of extracellular vesicles (EVs) in this process, as EVs obtained from cultured trophoblast spheroids incubated with endometrial cells induced down-regulation of all the three identified transcripts in endometrial cells. Finally, we show that EVs/nanoparticles captured from conditioned culture media of viable embryos as opposed to degenerating embryos induce ZNF81 down-regulation in endometrial cells, hinting at the functional importance of this intercellular communication. Conclusion: Ultimately, our findings demonstrate the existence of an RNA-based communication which may be of critical importance for the establishment of pregnancy.

Citation

Es-Haghi, M., Godakumara, K., Häling, A., Lättekivi, F., Lavrits, A., Viil, J., …Fazeli, A. (2019). Specific trophoblast transcripts transferred by extracellular vesicles affect gene expression in endometrial epithelial cells and may have a role in embryo-maternal crosstalk. Cell Communication and Signaling, 17(1), Article 146. https://doi.org/10.1186/s12964-019-0448-x

• Journal Article Type: Article
• Acceptance Date: Oct 4, 2019
• Online Publication Date: Nov 14, 2019
• Publication Date: Nov 14, 2019
• Deposit Date: Nov 19, 2019
• Publicly Available Date: Nov 19, 2019
• Journal: Cell Communication and Signaling
• Electronic ISSN: 1478-811X
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 1
• Article Number: 146
• DOI: https://doi.org/10.1186/s12964-019-0448-x
• Keywords: Cell Biology; Biochemistry; Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/3332085
• Publisher URL: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-019-0448-x