- Altmäe, Signe;
- Koel, Mariann;
- Võsa, Urmo;
- Adler, Priit;
- Suhorutšenko, Marina;
- Laisk-Podar, Triin;
- Kukushkina, Viktorija;
- Saare, Merli;
- Velthut-Meikas, Agne;
- Krjutškov, Kaarel;
- Aghajanova, Lusine;
- Lalitkumar, Parameswaran G;
- Gemzell-Danielsson, Kristina;
- Giudice, Linda;
- Simón, Carlos;
- Salumets, Andres
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.