An interactive analysis of the mouse oviductal miRNA profiles

Abstract

MicroRNAs are small non-coding molecules that control several cellular functions and act as negative post-transcriptional regulators of the mRNA. While their implication in several biological functions is already known, an important role as regulators of different physiological and pathological processes in fertilization and embryo development is currently emerging. Indeed, miRNAs have been found in the oviductal fluid packaged within the extracellular vesicles, which might act as natural nanoshuttles by transporting lipids, proteins, RNA molecules and miRNAs from the oviduct to the gametes or embryos. Here, an exhaustive bibliography search was carried out, followed by the construction of a computational model based on the networks theory in an attempt to recreate and elucidate the pathways potentially activated by the oviductal miRNA. The omics data published to date were gathered to create the Oviductal MiRNome, in which the miRNA target genes and their interactions are represented by using stringApp and the Network analyzer from Cytoscape 3.7.2. Then, the hyperlinked nodes were identified to investigate the pathways in which they are involved using the gene ontology enrichment analysis. To study the phenotypical effects after the removal of key genes on the reproductive system and embryo, knockout mouse lines for every protein-coding gene were investigated by using the International Mouse Phenotyping Consortium database. The creation of the Oviductal MiRNome revealed the presence of important genes and their interactions within the network. The functional enrichment analysis revealed that the hyperlinked nodes are involved in fundamental cellular functions, both structural and regulatory/signaling, suggesting their implication in fertilization and early embryo development. This fact was as well evidenced by the effects of the gene deletion in KO mice on the reproductive system and embryo development. The present study highlights the importance of studying the miRNA profiles and their enormous potential as tools to improve the assisted reproductive techniques currently used in human and animal reproduction.

Keywords: embryo development; extracellular vesicles; fertilization; gene; miRNA; miRnome; oviduct; reproduction.

FIGURE 1

Experimental design. The figure illustrates the steps followed during the development of the work. 1) we collected the oviductal miRNA from the literature and we obtained from the miRDB their experimentally verified targets. 2)The identified target genes were submitted to network creation in stringApp for Cytoscape 3.7.2.3) We performed an enrichment Gene Ontology and used the International Mouse Phenotyping Consortium to investigate the phenotypic impact on the reproductive system and embryo after the removal of important genes.

FIGURE 2

MiRNome_MC network. The figure shows the MiRNome Main Component (MiRNome_MC). The network was created with Cytoscape 3.7.2.