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Series GSE158958 Query DataSets for GSE158958
Status Public on Jul 01, 2021
Title Global transcriptomic changes occur in uterine fluid-derived extracellular vesicles (UF-EVs) during the endometrial window for embryo implantation
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Purpose: Extracellular vescicles (EVs) of uterine origin have recently been identified, but they are not comprised by current diagnostics on endometrial receptivity. In order to test the possibility to use EVs as biomarker reservoirs for non-invasive monitoring of the endometrial status, we defined two experimental designs: in step a) we aimed at assessing the concordance between the transcriptome of endometrial tissue and uterine fluid-derived EVs (UF-EVs); in step b) we aimed at unraveling the transcriptomic profile of UF-EVs released during the receptive phase and associated with successful implantation
Methods: RNAseq analysis was performed on total RNA isolated from a) endometrial biopsies and UF-EVs concomitantly collected from regularly cycling women; b) UF-EVs collected in the pre-receptive (LH+2) versus the receptive (LH+7) phase of provenly fertile women and in the receptive phase (LH+7) of women undergoing assisted reproduction and transfer of an euploid blastocyst. In the latter group, the outcomes of the following embryo transfer attempt were recorded, in order to compare the transcriptomic profile of women with successful versus failed implantation. Differential Gene Expression (DGE) and Gene Set Enrichment (GSEA) analyses were performed.
Results: In the first experimental design, a highly significant correlation was found between the transcriptional profiles of endometrial tissue biopsies and corresponding UF-EVs (r=0.71 p<0.001; ρ=0.65 p<0.001). In the second experimental design, using a large group of 73 samples, 16,777 genes were overall found to be expressed in UF-EVs. Of these, DGE analysis showed that 942 were up-regulated and 1,305 down-regulated during the receptive phase in women with proven fertility and 97 were up-regulated and 64 down-regulated during the receptive phase of women achieving successful implantation versus women failing to achieve pregnancy in the subsequent cycle. 41 genes had a statistically significant different expression in both comparisons. We additionally tested wether transcripts used by current endometrial receptivity tests based on endometrial biopsies (Endometrial Receptivity Assay, ERA test) could also be detected in UF-EVs: out of 238 ERA test gene data-set, GSEA highlighted 219 genes with similar transcriptional profile in UF-EVs. We then performed another comparison adding the list of genes consisting of the ‘metasignature’ transcriptome derived from the published meta-analysis of endometrial receptivity associated transcripts, comprising 57 genes. This last intersection identified 38 genes expressed in UF-EVs that i) show differential expression with the same transcriptional profile (same trends) in both EVs and ERA test assay; ii) belong to the leading edge of genes with the most significant enrichment score in our analysis; iii) are identified as receptivity-associated genes by the current meta-analysis on endometrial transcriptome.
Conclusions: This is the first study showing the capacity of UF-EVs to reflect the endometrial tissue transcriptional status and to establish a signature of genes expressed in UF-EVs that might serve as putative biomarkers for non-invasive endometrial receptivity tests.
 
Overall design Firstly In order to assess the concordance between endometrial tissue and uterine fluid-derived EVs (UF-EVs) transcriptome, we simultaneously sequenced RNA species derived from pairwise samples collected from physiologically cycling women (n=10 tissues and n=10 UF-EVs). Secondly, to unravel the transcriptomic profile of EVs released by the endometrium during the window of implantation, we analyzed RNA species of UF-EVs collected from a) provenly fertile women (LH+2 n=13 and LH+7 n=13) and b) a larger population of women undergoing ART and transfer of euploid blastocysts, as a function of pregnancy outcomes (n=49). .
 
Contributor(s) Giacomini E, Scotti G, Lazarevic D, Makieva S, Privitera L, Signorelli S, Pagliardini L, Cantone L, Bollati V, Papaleo E, Candiani M, Tonon G, Viganò P
Citation(s) 34190319
Submission date Oct 02, 2020
Last update date Jul 02, 2021
Contact name Giulia Maria Scotti
E-mail(s) giulis.scotti@gmail.com
Organization name San Raffaele Scientific Institute
Department Center for Omics Sciences
Street address via Olgettina, 60
City Milan
State/province Milan
ZIP/Postal code 20132
Country Italy
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (93)
GSM4816442 T22
GSM4816443 T25
GSM4816444 T26
Relations
BioProject PRJNA667091
SRA SRP286208

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE158958_counts_exp1.txt.gz 756.1 Kb (ftp)(http) TXT
GSE158958_counts_exp2.txt.gz 2.7 Mb (ftp)(http) TXT
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Processed data are available on Series record

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