Associations between PM_2.5 components, temperature, and semen quality: Insights from seminal plasma metabolome

Declining semen quality has become a global concern, with environmental exposures implicated as key contributors. In this prospective cohort study of 649 men in Wuhan, China, we investigated associations between fine particulate matter (PM_2.5) components, ambient temperature, and semen quality, and explored underlying mechanisms using untargeted seminal plasma metabolomics. Bayesian Kernel Machine Regression and generalized linear models revealed that higher exposures to nitrate (NO₃^-), sulfate (SO₄^2-), and temperature were independently associated with reduced sperm concentration. Specifically, a 2.72-fold increase in NO₃^-, SO₄^2-, and temperature corresponded to decreases of 19.41 × 10⁶/mL, 47.89 × 10⁶/mL, and 36.05 × 10⁶/mL in sperm concentration, respectively. Metabolomic profiling identified distinct metabolic signatures associated with each exposure: SO₄^2- and temperature predominantly disrupted lipid metabolism, while NO₃^- exposure primarily disrupted nucleotide metabolism. Notably, three metabolites-3-hydroxybutyrylcarnitine, eicosapentaenoic acid, and uridine-were consistently linked to all exposures, indicating shared pathways involving mitochondrial dysfunction, membrane instability, and oxidative stress. These findings provide molecular evidence that co-occurring environmental stressors can impair male reproductive health via convergent metabolic mechanisms, highlighting the importance of addressing both individual and combined exposure risks.