摘要：Graphical abstractIntegrative analysis of testicular genome-wide DNA methylome and transcriptome identified key genes and pathways related to steroidogenesis and spermatogenesis processes, which may be the DNA methylation-regulated mechanism in male reproductive impairment caused by PM2.5.Display OmittedAbstractThe effects of ambient fine particles on male reproductive health have raised widespread concern. The particular underlying mechanisms of the damage remain largely unclear and demand more research in new directions. Previous research has revealed that DNA methylation plays an important role in male reproductive development and is also vulnerable to environmental influences. However, there hasn't been enough investigation into the involvement of DNA methylation in PM2.5-induced male reproductive toxicity. Here, we establish a real-time PM2.5exposure model and revealed that PM2.5exposure could lead to testicular dysfunction including spermatogenesis impairment and steroid hormone dysfunction. In particular, the decrease in the testicular global level of 5-methylcytosine (5mC) indicated a possible association of DNA methylation with testicular injury induced by PM2.5exposure. Further genome-wide methylation analysis revealed genomic hypomethylation of testicular DNA and identified more than 1000 differentially methylated regions in both CAP and UA versus FA, indicating that PM2.5exposure, even low-dose, could modulate the testicular methylome. Furthermore, integrated analysis of methylome and transcriptome identified some key methylated genes and networks, which may be involved in spermatogenesis and synthesis of steroid hormone. The testicular methylation levels of key genes especiallyCyp11a1andPax8raised, and their consequent reduced expression may impair the testosterone and sperm production process. Our research provides fundamental knowledge as well as novel insights into the possible involvement of DNA methylation in PM2.5-induced male reproductive harm.
