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

Background: Heavy metal exposure induces oxidative stress, which is critical for adverse male reproductive health.

Objective: To explore the mediating effect of oxidative stress on the relationship of heavy metal exposure with semen quality.

Methods: 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.

Results: 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 (p_trend < 0.001), between urinary 8-isoPGF2α levels and total motility (p_trend = 0.052), progressive motility (p_trend = 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-isoPGF_2α, 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.

Conclusions: 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-isoPGF_2α 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.