Real-world PM2.5 exposure triggers early testicular epigenetic responses in the absence of significant changes in measured reproductive endpoints.

Background

Industrialization has led to widespread air pollution, among which particulate matter ≤ 2.5 μm (PM2.5) represents a significant environmental pollutant associated with various adverse health outcomes. Emerging evidence indicates that the male reproductive system is a sensitive target organ of PM2.5 toxicity; however, the temporal progression of early biological responses before measurable reproductive changes become apparent remains insufficiently investigated.

Methods

Here, male mice were exposed to real-world ambient PM2.5 in Hangzhou using a whole-body inhalation system for 4, 8, or 12 weeks, enabling longitudinal assessment of testicular responses across approximately one to three spermatogenic cycles.

Results

Despite the absence of significant changes in sperm quality, reproductive hormone levels, histopathology, or oxidative DNA damage, testicular global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) showed significant time-dependent changes. Specifically, global 5mC decreased after 4 weeks of PM2.5 exposure but increased after 12 weeks compared to controls (P < 0.05). Within the PM2.5-exposed groups, 5mC levels were also higher at 12 weeks than at 4 weeks (P < 0.05). For 5hmC, the decrease observed at 4 weeks was not significant, whereas 5hmC levels increased significantly after 12 weeks compared to controls and with the 4-week PM2.5-exposed group (P < 0.05).

Conclusions

These findings indicate that testicular epigenetic remodeling is an early and sensitive molecular response to real-world PM2.5 exposure, detected in the absence of significant changes in the reproductive endpoints assessed in this study.