Epigenetic aging of semen is associated with inflammation

Male infertility has been a primary cause of global infertility, affecting 8–12% of couples worldwide. Previous studies have shown that semen quality decreases with advanced aging with an increased presence of inflammatory cells. In this study, we examined changes in the epigenome across a diverse cohort that includes both fertile and infertile men. We also compare the age-associated changes in semen to those observed in buccal swabs in order to characterize differences in epigenetic aging across diverse tissues. We found that variations in the semen methylome associated with aging are linked to inflammatory genes. Many age-associated sites are demethylated with advanced aging and are associated with the activation of inflammatory pathways. By contrast, we do not observe age-associated changes in inflammatory genes in buccal swab methylomes, which instead are characterized by changes to bivalent promoters. Our findings highlight the potential of epigenetic markers as indicators of male reproductive health.

男性不育已成为全球不孕不育的主要诱因，影响全球8%至12%的育龄夫妇。既往研究表明，精液质量随衰老进程逐渐下降，且炎症细胞的检出率随之升高。本研究针对包含生育正常男性与不育男性的多样化队列，分析了其表观基因组（epigenome）的变化特征；同时将精液中与年龄相关的表观遗传变化，与口腔拭子中的同类变化进行对比，以明确不同组织间表观遗传衰老的差异特征。研究发现，精液甲基化组（methylome）中与衰老相关的变异，与炎症相关基因存在关联：大量与衰老相关的甲基化位点在衰老进程中发生去甲基化，且与炎症通路的激活密切相关。与之形成鲜明对比的是，口腔拭子甲基化组中并未观测到炎症相关基因随衰老产生的变化，其表观遗传特征主要体现为二价启动子（bivalent promoters）的改变。本研究结果凸显了表观遗传标志物作为男性生殖健康评估指标的潜在应用价值。