Altered microRNA expression profiles of human spermatozoa in normal fertile men of different ages

Abstract

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20–30 years; Group B, n = 10, age: 31–40 years; and Group C, n = 9, age: 41–55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics

“…Exposure to MPs/NPs activates the Hippo and MAPK signaling pathways, influencing cell proliferation and causing reproductive toxicity in mice. , Our sequencing data indicated significant changes in several miRNAs linked to reproductive genetics. Enrichment analysis revealed that age-related miRNAs, such as mmu-miR-1983 and mmu-miR-5100, which are strongly associated with the Hippo and MAPK signaling pathways, were downregulated, suggesting that male fertility declines with increasing age . In addition, our study found that mmu-miR-1983 and mmu-miR-5100 were significantly associated with genes related to reproductive toxicity, potentially affecting the Hippo and MAPK signaling pathways.…”

“…Enrichment analysis revealed that agerelated miRNAs, such as mmu-miR-1983 and mmu-miR-5100, which are strongly associated with the Hippo and MAPK signaling pathways, were downregulated, suggesting that male fertility declines with increasing age. 57 In addition, our study found that mmu-miR-1983 and mmu-miR-5100 were significantly associated with genes related to reproductive toxicity, potentially affecting the Hippo and MAPK signaling pathways. A pronounced decrease in mmu-miR-6240 levels was observed in F 0 sperm with exposure to particulate matter with a diameter of less than 2.5 μm (PM 2.5 ), which could lead to intergenerational primary hypogonadism in offsprings.…”

Exploring Differentially Expressed Sperm miRNAs in Idiopathic Recurrent Pregnancy Loss and Their Association with Early Embryonic Development

“…miRNAs are pivotal in influencing age-related changes in male fertility and may provide valuable insights into the mechanisms driving the decline in fertility as men age. Zhao et al analyzed changes in miRNA expression profiles of human spermatozoa and discovered that hsa-miR-7977 expression increases with age [ 41 ]. This finding suggests that elevated hsa-miR-7977 levels may be linked to poor sperm quality.…”