%0 Journal Article
%A Altmäe, Signe
%A Koel, Mariann
%A Võsa, Urmo
%A Adler, Priit
%A Suhorutšenko, Marina
%A Laisk-Podar, Triin
%A Kukushkina, Viktorija
%A Saare, Merli
%A Velthut-Meikas, Agne
%A Krjutškov, Kaarel
%A Aghajanova, Lusine
%A Lalitkumar, Parameswaran G
%A Gemzell-Danielsson, Kristina
%A Giudice, Linda
%A Simón, Carlos
%A Salumets, Andres
%T Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers.
%D 2017
%U http://hdl.handle.net/10668/11544
%X 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.
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