Abstract：
Genetic and epigenetic changes in sperm caused by male aging may be essential factors affecting semen parameters, but the effects and specific molecular mechanisms of aging on male reproduction have not been fully clarified. In this study, to explore the effect of aging on male fertility and seek the potential molecular etiology, we performed high-throughput RNA-sequencing in isolated spermatogenic cells, including pachytene spermatocytes (marked by the completion of chromosome synapsis) and round spermatids (produced by the separation of sister chromatids) from the elderly and the young men. Functional enrichment analysis of differentially expressed genes (DEGs) in round spermatids between the elderly and young showed that they were significantly enriched in gamete generation, spindle assembly, and cilium movement involved in cell motility. In addition, the expression levels of DEGs in round spermatids (post-meiotic cells) were found to be more susceptible to age. Furthermore, ten genes (AURKA, CCNB1, CDC20, CCNB2, KIF2C, KIAA0101, NR5A1, PLK1, PTTG1, RAD51AP1) were identified to be the hub genes involved in the regulation of sperm quality in the elderly through Protein-Protein Interaction (PPI) network construction and measuring semantic among GO terms and gene products. Our data provide aging-related molecular alterations in meiotic and post-meiotic spermatogenic cells, and the information gained from this study may explain the abnormal aging-related male fertility decline.
摘要：
男性衰老引起的精子遗传和表观遗传变化可能是影响精液参数的重要因素，但是衰老对男性生殖的影响和特定的分子机制尚未完全阐明。在这项研究中,探讨衰老对男性生育力的影响，寻找潜在的分子病因，我们在分离的生精细胞中进行了高通量RNA测序，包括来自老年人和年轻人的粗线精母细胞（以完成染色体突触为标志）和圆形精子细胞（由姐妹染色单体分离产生）。对中老年人和年轻人圆形精子细胞中差异表达基因(DEGs)的功能富集分析表明,主轴总成,纤毛运动与细胞运动有关。此外,发现圆形精子细胞（减数分裂后细胞）中DEGs的表达水平更容易受到年龄的影响。此外，十个基因（AURKA，CCNB1,CDC20,CCNB2,KIF2C,KIAA0101，NR5A1，PLK1，PTTG1，RAD51AP1）通过蛋白质-蛋白质相互作用（PPI）网络构建并测量GO术语和基因产物之间的语义，被鉴定为参与调节老年人精子质量的枢纽基因。我们的数据提供了减数分裂和减数分裂后生精细胞的衰老相关分子改变，从这项研究中获得的信息可能解释了与衰老相关的异常男性生育力下降。
