MicroRNAs Secreted by the Embryo in Spent Culture Medium Can Regulate mRNAs Involved in Endometrial Receptivity, Embryo Attachment, and Invasion

MicroRNAs, secreted by the embryo in blastocoel fluid (BF) and embryo spent culture medium (SCM), regulate important cellular pathways controlling the stemness of inner cell mass, trophectoderm differentiation, and the dialogue between blastocyst and maternal tissues. In recent years, their role as non-invasive biomarkers of embryo quality has been deeply investigated. We compared the expression profiles of 96 microRNAs between BF and SCM from the same embryos, highlighting the differences between these two compartments. We found 10 and 6 microRNAs specifically expressed in BF and in SCM, respectively; 22 microRNAs significantly up-regulated in BF; and 2 significantly up-regulated in SCM. To investigate the role of SCM microRNAs in implantation, we focused on the microRNAs specifically expressed/up-regulated in SCM and absent in blank medium. We deepened our understanding of SCM microRNA's biological role by building a network of miRNA-mRNA interaction within the signalling pathways crucial in embryo implantation success. We demonstrated that BF and SCM contain different sets of microRNAs playing different and unique roles in embryo implantation and development. Finally, we suggest that there is not a single "ideal" technique to identify the most competent embryo, but an integrated approach is needed to obtain informative results on the health of the embryo.