衰老对男性生殖健康的影响及其对后代的影响正在得到越来越广泛的认可。研究父辈年龄和后代健康状况的相关流行病学研究表明,年龄较大的父亲的孩子中遗传性疾病的发生率更高。鉴于父系年龄相关疾病的遗传基础,我们的目的是表征发育中的生殖细胞的基因表达。从年轻(平均5.3个月)和老年(平均19.5个月)的棕色挪威大鼠中收集圆形精子细胞(RS),代表20-30岁和55岁以上的人类,分别。通过mRNA测序获得基因表达数据(n=5),并分析差异表达。测序数据显示老年大鼠RS中211个上调和9个下调的转录本,与年轻相比(log2FC>1,p<0.05)。表达增加的转录本涉及几个过程,包括精子运动/形态,精子-卵子结合,获能,和表观遗传。此外,有许多失调的转录本调节生殖细胞表观遗传标记和支持生殖细胞结合和通讯。这些结果表明,RS基因表达随着年龄的增长而总体增加,生精功能受到干扰。一起来看,这些发现有助于确定生育能力的遗传起源,生殖细胞生态位,和表观遗传效应观察到晚期父系衰老。
The effects of aging on the reproductive health of men and the consequences for their offspring are becoming more widely recognized. Correlative epidemiological studies examining paternal age and offspring health suggest there are more frequent occurrences of genetic disorders in the children of older fathers. Given the genetic basis for paternal age-related disorders, we aim to characterize gene expression in developing germ cells. Round spermatids (RS) were collected from young (mean = 5.3 months) and aged (mean = 19.5 months) Brown Norway rats, representative of humans aged 20-30 years and 55+ years, respectively. Gene expression data were obtained by mRNA sequencing (n = 5), and were analysed for differential expression. Sequencing data display 211 upregulated and 9 downregulated transcripts in RS of aged rats, compared to young (log2FC >1, p < 0.05). Transcripts with increased expression are involved in several processes including sperm motility/morphology, sperm-egg binding, capacitation, and epigenetic inheritance. In addition, there are numerous dysregulated transcripts that regulate germ cell epigenetic marks and Sertoli-germ cell binding and communication. These results show an overall increase in RS gene expression with age, with spermatogenic functions being perturbed. Taken together, these findings help identify the genetic origin of the fertility, germ cell niche, and epigenetic effects observed with advanced paternal aging.