Associations of seminal plasma metal mixtures with sperm quality parameters and exploratory mediation analysis of urinary oxidative stress biomarkers: a cross-sectional study from the RHCC-AC preconception cohort.

Background: There is increasing concern over the global decline in semen quality. However, the role of environmental metal exposure remains uncertain, and the underlying mechanisms are poorly understood. Methods: A cross-sectional cohort study included 425 men from the Reproductive Health of Childbearing Couples-Anhui Cohort (RHCC-AC). Seventeen metals in seminal plasma were quantified by ICP-MS. Eight urinary oxidative stress biomarkers were measured by UPLC-MS/MS. Sperm quality parameters included sperm concentration, progressive motility, total motility, abnormality rate, and sperm DNA fragmentation index (DFI). Weighted quantile sum (WQS) regression was applied to assess single and joint effects of metal mixtures. In addition, exploratory mediation analysis was conducted to examine the potential mediating role of oxidative stress in the associations between metal exposure and sperm quality. Results: Single-metal analyses showed that Al was positively associated with sperm abnormality rate, whereas Co and Cu were inversely associated with progressive and total motility. As, Fe, and Se were positively associated with sperm concentration. In mixture analyses, Al was the primary contributor to increased sperm abnormality rate (positive-direction WQS: Conclusion: Seminal plasma metal mixtures, particularly Al and Co, were associated with sperm quality. Exploratory mediation analysis suggested potential indirect effects of D,L-o-tyrosine in the associations of Hg and V with sperm concentration, but these findings should be interpreted cautiously. Further studies using seminal or reproductive tract-specific oxidative stress biomarkers are warranted to clarify the role of oxidative stress in linking metal exposure to male reproductive system injury.