Meta-signature of human endometrial receptivity : a meta-analysis and validation study of transcriptomic biomarkers

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Altmae , S , Koel , M , Vosa , U , Adler , P , Suhorutsenko , M , Laisk-Podar , T , Kukushkina , V , Saare , M , Velthut-Meikas , A , Krjutskov , K , Aghajanova , L , Lalitkumar , P G , Gemzell-Danielsson , K , Giudice , L , Simon , C & Salumets , A 2017 , ' Meta-signature of human endometrial receptivity : a meta-analysis and validation study of transcriptomic biomarkers ' , Scientific Reports , vol. 7 , 10077 . https://doi.org/10.1038/s41598-017-10098-3

Title: Meta-signature of human endometrial receptivity : a meta-analysis and validation study of transcriptomic biomarkers
Author: Altmae, Signe; Koel, Mariann; Vosa, Urmo; Adler, Priit; Suhorutsenko, Marina; Laisk-Podar, Triin; Kukushkina, Viktorija; Saare, Merli; Velthut-Meikas, Agne; Krjutskov, Kaarel; Aghajanova, Lusine; Lalitkumar, Parameswaran G.; Gemzell-Danielsson, Kristina; Giudice, Linda; Simon, Carlos; Salumets, Andres
Contributor: University of Helsinki, Clinicum
Date: 2017-08-30
Language: eng
Number of pages: 15
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/224334
Abstract: Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up-and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from 'pre-receptive' and 88 from mid-secretory, 'receptive' phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.
Subject: GENE-EXPRESSION ANALYSIS
IMPLANTATION FAILURE
MENSTRUAL-CYCLE
ALPHA-V-BETA-3 INTEGRIN
EMBRYO IMPLANTATION
EUTOPIC ENDOMETRIUM
UTERINE RECEPTIVITY
MICRORNA EXPRESSION
HORMONAL-REGULATION
CANDIDATE GENES
3123 Gynaecology and paediatrics
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