Exposure to ambient fine particulate matter (PM) has been linked to a decline in semen quality, but the underlying mechanisms for this association remain unclear. We aimed to examine whether specific metabolites act as mediators in the association between PM exposure and changes in semen quality. We conducted untargeted metabolomics analysis using LC-MS/MS platforms to identified seminal plasma metabolites associated with various semen quality parameters among 200 Chinese adult men. Additionally, we performed mediation analyses to examine the effects of the seminal plasma metabolites on the association between PM exposure and semen quality. We identified 140 differential metabolites between the normal and abnormal semen groups, involving two metabolic pathways: Alanine, aspartate and glutamate metabolism, and Aminoacyl-tRNA biosynthesis. We additionally identified 7 specific seminal plasma metabolites that were associated with discrepant metabolic networks related to semen quality. The mediation analysis revealed that D-Aspartate might play a mediating role in the adverse effects of ambient PM exposure on both total and progressive motility during spermatogenesis period (70-90 days before ejaculation), with a proportion of mediation up to 16% and 17%, respectively. Exposure to PM was associated with alterations in D-Aspartate levels, which might partially mediate the association between PM and reduced sperm motility.
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