Study On The Roles Of Mitochondria-related MiR-574 On Sperm In Aging Male

Objective:Couples are delaying childbearing in recent decades.While women experience a notable decrease in oocyte production in their late thirties,the effect of advanced paternal age on reproduction is incompletely understood.Herein,we observed that numerous miRNAs,including miR-574,increased in the sperm of aging males,as indicated by high-throughput sequencing.In order to confirm the specific protective effect of miR-574 in aging males,we look for miR-574 target gene and explore a fresh view to comprehend the aging process in sperm.Method:To confirm the small RNA-seq results,we established two aging mouse models:the natural aging mouse model and a D-gal-induced aging mouse model by injecting D-gal subcutaneously into the mice daily for 42 days.Moreover,we collected clinical semen samples and detected the expression of miR-574 in the sperm of patients more than or less than 40 years old.We predicted the target genes of miR-574 within the mitochondrial pathway by the bioinformatics tool RNA22 and found an evolutionarily conserved target site in the mt-ND5 gene.Results:Mitochondria-related miR-574 was upregulated in the sperm of aging males and was related to poor sperm motility.MiR-574 impaired mitochondrial function and reduced cellular ATP production.MiR-574 depletion relieved mitochondrial dysfunction and increased cellular ATP production.MiR-574 regulated mitochondrial function by directly targeting mt-ND5.Conclusion:Our study delineates a miR-574-ND5 module that regulates mitochondrial function and ATP generation with respect to functional implications in the sperm of aging males.This shows that miR-574 plays important roles in sperm function and the regulatory signaling might offer a fresh view to comprehend the aging process in sperm.