Publicación

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

  • SCIENTIFIC REPORTS
  • Autores
    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, PG; Gemzell-Danielsson, K; Giudice, L; Simon, C; Salumets, A
  • Año Publicación
    2017
  • Volumen
    7

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.


Web financiada por la Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, Fondo Europeo de Desarrollo Regional (FEDER), proyecto SOMM17/6107/UG

Web financiada por la Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, Fondo Europeo de Desarrollo Regional (FEDER), proyecto SOMM17/6107/UGR