期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms19041233
关键词
testosterone deficiency; sperm motility; apoptosis; miRNA; exosome
资金
- National Natural Science Foundation of China [31530073, 31601918, 31772576, 31522055]
- Sichuan Province & Chinese Academy of Science of Science & Technology Cooperation Project [2017JZ0025]
- Program for Innovative Research Team of Sichuan Province [2015TD0012]
- Science & Technology Support Program of Sichuan [2016NYZ0042]
- Science & Technology Major Projects of Sichuan [2017NZDZX0002]
- Earmarked Fund for China Agriculture Research System [CARS-35-01A]
- District-School cooperation project from Yucheng District, Ya'an City, Sichuan Province, China
Recent evidence suggests that testosterone deficiency can dramatically decrease the quality of sperm. MicroRNAs (miRNAs) are conserved mediators of post-transcriptional gene regulation in eukaryotes. However, the systemic regulation and function of miRNAs in sperm quality decline induced by testosterone deficiency has not been investigated. Here, we found that the sperm apoptosis was significantly enhanced and the sperm motility was dramatically decreased in hemicastrated pigs. We then used small RNA sequencing to detect miRNA profiles of sperm from pigs with prepubertal hemicastration (HC) and compared them with control libraries. We identified 16 differentially expressed (DE) miRNAs between the sperm of prepubertal HC and control (CT) pigs. Functional enrichment analysis indicated that the target genes of these DE miRNAs were mainly enriched in apoptosis-related pathways including the p53, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. Furthermore, gain-and loss-of-function analyses demonstrated potential anti-apoptotic effects of the DE miRNAs miR-26a-5p and let-7g-5p on sperm cells. The luciferase reporter assay confirmed that PTEN and PMAIP1 are targets of miR-26a-5p and let-7g-5p, respectively. Spearman's correlation analysis revealed significantly positive correlations between the sperm and its corresponding seminal plasma exosomes regarding the miRNA expression levels. In conclusion, testosterone deficiency-induced changes in the miRNA components of seminal plasma exosomes secreted by the genital tract may partially elucidate sperm miRNAome alterations, which are further responsible for the decline of sperm motility.
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