Differentially Expressed Key miRNAs and Potential Targets Analysis in Asthenzoospermia
Objective:Asthenozoospermia,a condition observed in 40％of infertile males,is characterized by reduced sperm motility.MicroRNAs(miRNAs)play a pivotal role in spermatogenesis,yet their involvement in asthenozoospermia remains poorly understood.This study aims to elucidate the molecular mechanisms of miRNAs in asthenozoospermia.Method(s):Sperm samples were collected from individuals with severe asthenozoospermia and healthy males.High-throughput sequencing was employed to identify differentially expressed miRNAs,followed by bioinformatics analysis of these significant miRNAs.The altered expression of two specific miRNAs and their target genes was confirmed using qRT-PCR.Result(s):When comparing severe asthenozoospermia patients to healthy males,146 miRNAs exhibited significant alterations(P＜0.05;|log2 Fold Change|＞1),with 52 upregulated and 94 downregulated miRNAs.The ten most significantly upregulated and downregulated miRNAs were subjected to target gene prediction through the miRDB and TargetScan databases,a total of 1407 target genes were found to be supported by both databases.Enrichment analysis revealed that miRNA target genes were enriched in sperm cell processes,and they were involved in oxidative metabolism,stimulus response,proliferation,differentiation,and apoptosis in sperm cells.Pathway analysis indicated that target genes might participate in processes such as autophagy,cellular senescence,the PI3K-Akt signaling pathway,the MAPK signaling pathway,the HIF-1 signaling pathway,and the mTOR signaling pathway.Notably,among the specifically upregulated miRNAs in ast henozoospermia,hsa-miR-371a-5p and hsa-miR-2355-5p were identified,with their respective target genes being the autophagy effector protein Beclinl and mitochondrial inner membrane protein prohibitin2(PHB2),both directly involved in mitochondrial autophagy.qRT-PCR results demonstrated an increased expression of hsa-miR-371a-5p and hsa-miR-2355-5p in sperm as motility declined.Conclusion(s):This study identified miRNAs with specific dysregulation in the sperm of asthenozoospermia patients and their target genes,offering new insights and a theoretical basis for further investigation into the mechanisms by which miRNAs regulate mitochondrial autophagic functions in low motility sperm.
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