Identification of biomarkers of male infertility through the circRNA expression profiling of seminal plasma

Circular RNAs (circRNAs) are key regulators of reproductive biology. However, limited information is available regarding circRNA expression profiles in seminal plasma samples from individuals with male infertility. The present study aimed to identify circRNAs associated with infertility in seminal plasma samples and to clarify their potential as biomarkers, as well as the possible molecular mechanisms underlying their functions. Next-generation RNA sequencing was conducted to analyze circRNA profiles in seminal plasma from healthy controls, oligoasthenospermia (OAZ) patients, and non-obstructive azoospermia (NOA) patients. Bioinformatics analysis revealed that 637 circRNAs were differentially expressed between OAZ and control subjects, as well as 272 circRNAs that were differentially expressed between NOA and control subjects. The expression of key circRNAs ( hsa-SAP130_0002, hsa-TRPC1_0001, hsa-FBRS_0001, hsa-ACACA_0025, hsa-UTRN_0042, and hsa-ZNF532_0023) was then validated by qPCR, and their diagnostic accuracy for infertility was confirmed through ROC curve analysis. Additionally, possible circRNA-miRNA-mRNA regulatory networks were developed for these candidate biomarkers. Collectively, this study identifies a novel set of circRNAs with potential as diagnostic biomarkers for male infertility and provides molecular insights that may facilitate both diagnostic and therapeutic efforts.