Functional prediction and profiling of exosomal circRNAs derived from seminal plasma for the diagnosis and treatment of oligoasthenospermia

Oligoasthenospermia (OAZ) is the most common element contributing to male infertility. However, the etiology of OAZ remains unknown in the majority of cases. Growing evidence indicates that exosomal circular (circ)RNAs may exhibit potential as biological markers for the detection of various disorders. The available information on exosomes derived from seminal plasma is limited. The present study investigated the composition and role of circRNAs in exosomes isolated from seminal plasma of patients with OAZ. Exosomes were isolated from the seminal plasma of 12 patients with OAZ and 12 matched healthy controls. Thereafter, RNA sequencing was performed using exosomes from both groups to identify circRNAs associated with OAZ. The sequencing data revealed a total of 14,991 circRNAs. Among these, 7,635 were upregulated and 7,356 were downregulated in patients with OAZ. Gene Ontology functional enrichment analysis revealed that the differentially expressed exosomal circRNAs were primarily enriched in ‘protein binding’, ‘intracellular organelles’ and ‘cellular metabolism’. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed exosomal circRNAs were enriched in ‘ubiquitin-mediated proteolysis’, ‘endocytosis’ and ‘RNA transport’, which are involved in spermatogenesis-related pathways. Then seven differentially expressed circRNAs were predicted and validated as putative upstream targets and their target genes also were detected by reverse transcription-quantitative PCR. CircRNA-microRNA-mRNA network was constructed to predict their potential functions. The findings provide a preliminary foundation for identifying the potential diagnostic value of critical exosomal circRNAs involved in OAZ.