Expression profiling and function analysis identified new cumulus cells-expressed genes and miRNAs predictive of oocyte developmental potential

Although studies have identified cumulus cells (CCs)-expressed genes/miRNAs that regulate cumulus expansion and/or CC apoptosis and may be used as markers for selection of competent oocytes/embryos, CCs-expressed genes/miRNAs whose expression levels are directly correlated with oocyte developmental potential (DP) are urgently needed. To identify CCs-expressed DP-directly-related genes/miRNAs, we first established CC models from mouse cumulus-oocyte-complexes that showed significantly different DP after maturation in vitro or in vivo. By conducting mRNA/miRNA sequencing and functional analysis using such in vitro and in vivo CC models, we identified and validated new sets of CCs-expressed genes/miRNAs, whose expression levels were directly correlated with oocyte DP. Thus, we identified and validated Spp1, Fn1, Sdc1 and Ngf as DP-beneficial genes, Fos and Jun as DP-detrimental genes, and miR-7686-5p, miR-133a-3p, novel-miR-239, novel-miR-193 and miR-339-5p as DP-detrimental miRNAs. Furthermore, the close similarities in top KEGG pathways among 4 different experiments suggest that CCs-expressed genes and/or miRNAs regulate oocyte DP mostly indirectly through regulating cumulus expansion and/or CC apoptosis. The new genes/miRNAs identified can be used as markers for selection of competent oocytes/embryos, and the data will contribute to elucidating oocyte maturation mechanisms.