Heavy metal exposure, oxidative stress and semen quality: Exploring associations and mediation effects in reproductive-aged men

Heavy metal exposure induces oxidative stress, which is critical for adverse male reproductive health. To explore the mediating effect of oxidative stress on the relationship of heavy metal exposure with semen quality. Urinary levels of three oxidative stress markers, semen quality, and urinary arsenic, cadmium and lead were examined among 1020 men. Multivariate linear regression was applied to explore cross-sectional associations, and the role of oxidative stress as mediators was investigated. Quartiles of metals showed significant dose-dependent relationships with increasing levels of 8-hydroxy-2deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA). Significant or suggestive associations were also found between urinary 8-OHdG levels and the percentage of normal sperm morphology (ptrend < 0.001), between urinary 8-isoPGF2α levels and total motility (ptrend = 0.052), progressive motility (ptrend = 0.050) respectively. The mediation analysis showed that about 14.59%, 18.06%, 15.35% or 16.49% of the association between arsenic/cadmium exposure and the decreased total motility/progressive motility was mediated by 8-isoPGF2α, respectively. In addition, about 16.47% of the relationship between lead exposure and the decreased percentage of normal sperm morphology was mediated by 8-OHdG. Our findings suggest that higher urinary arsenic, cadmium and lead levels were associated with increased oxidative stress markers, which also related with altered semen quality. 8-isoPGF2α and 8-OHdG might be the possible mediators of the associations between urinary heavy metals and total motility, progressive motility or the proportion of normal sperm morphology.