NDLI: Trophoblast derived extracellular vesicles specifically alter the transcriptome of endometrial cells and may constitute a critical component of embryo-maternal communication

Content Provider	Springer Nature : BioMed Central
Author	Godakumara, Kasun Ord, James Lättekivi, Freddy Dissanayake, Keerthie Viil, Janeli Boggavarapu, Nageswara Rao Faridani, Omid R Jääger, Kersti Velthut-Meikas, Agne Jaakma, Ülle Salumets, Andres Fazeli, Alireza
Abstract	Background The period of time when the embryo and the endometrium undergo significant morphological alterations to facilitate a successful implantation—known as “window of implantation”—is a critical moment in human reproduction. Embryo and the endometrium communicate extensively during this period, and lipid bilayer bound nanoscale extracellular vesicles (EVs) are purported to be integral to this communication. Methods To investigate the nature of the EV-mediated embryo-maternal communication, we have supplemented trophoblast analogue spheroid (JAr) derived EVs to an endometrial analogue (RL 95–2) cell layer and characterized the transcriptomic alterations using RNA sequencing. EVs derived from non-trophoblast cells (HEK293) were used as a negative control. The cargo of the EVs were also investigated through mRNA and miRNA sequencing. Results Trophoblast spheroid derived EVs induced drastic transcriptomic alterations in the endometrial cells while the non-trophoblast cell derived EVs failed to induce such changes demonstrating functional specificity in terms of EV origin. Through gene set enrichment analysis (GSEA), we found that the response in endometrial cells was focused on extracellular matrix remodelling and G protein-coupled receptors’ signalling, both of which are of known functional relevance to endometrial receptivity. Approximately 9% of genes downregulated in endometrial cells were high-confidence predicted targets of miRNAs detected exclusively in trophoblast analogue-derived EVs, suggesting that only a small proportion of reduced expression in endometrial cells can be attributed directly to gene silencing by miRNAs carried as cargo in the EVs. Conclusion Our study reveals that trophoblast derived EVs have the ability to modify the endometrial gene expression, potentially with functional importance for embryo-maternal communication during implantation, although the exact underlying signalling mechanisms remain to be elucidated.
Related Links	https://rbej.biomedcentral.com/counter/pdf/10.1186/s12958-021-00801-5.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14777827
DOI	10.1186/s12958-021-00801-5
Journal	Reproductive Biology and Endocrinology
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2021-07-21
Access Restriction	Open
Subject Keyword	Reproductive Medicine Endocrinology Embryo-maternal communication Extracellular vesicles miRNA signalling RNA-sequencing
Content Type	Text
Resource Type	Article
Subject	Endocrinology Obstetrics and Gynecology Developmental Biology Reproductive Medicine
Journal Impact Factor	4.2/2023
5-Year Journal Impact Factor	5.3/2023

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