Altmäe, SigneKoel, MariannVõsa, UrmoAdler, PriitSuhorutšenko, MarinaLaisk-Podar, TriinKukushkina, ViktorijaSaare, MerliVelthut-Meikas, AgneKrjutškov, KaarelAghajanova, LusineLalitkumar, Parameswaran GGemzell-Danielsson, KristinaGiudice, LindaSimón, CarlosSalumets, Andres2023-01-252023-01-252017-08-30http://hdl.handle.net/10668/11544Previous 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AdultBiomarkersComputational BiologyEmbryo ImplantationEndometriumExosomesFemaleFertilityGene Expression ProfilingGene OntologyGene Regulatory NetworksHumansImmunity, InnateMenstrual CycleMicroRNAsMolecular Sequence AnnotationRNA, MessengerSequence Analysis, RNATranscriptomeresearch article28855728open access10.1038/s41598-017-10098-32045-2322PMC5577343https://www.nature.com/articles/s41598-017-10098-3.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577343/pdf