Cadmium, Lead, and Other Metals in Relation to Semen Quality: Human Evidence for Molybdenum as a Male Reproductive Toxicant

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Abstract
Evidence on human semen quality as it relates to exposure to various metals, both essential (e.g., zinc, copper) and nonessential (e.g., cadmium, lead), is inconsistent. Most studies to date used small sample sizes and were unable to account for important covariates. Our goal in this study was to assess relationships between exposure to multiple metals at environmental levels and human semen-quality parameters. We measured semen quality and metals in blood (arsenic, Cd, chromium, Cu, Pb, manganese, mercury, molybdenum, selenium, and Zn) among 219 men recruited through two infertility clinics. We used multiple statistical approaches to assess relationships between metals and semen quality while accounting for important covariates and various metals. Among a number of notable findings, the associations involving Mo were the most consistent over the various statistical approaches. We found dose-dependent trends between Mo and declined sperm concentration and normal morphology, even when considering potential confounders and other metals. For example, adjusted odds ratios (ORs) for below-reference semen-quality parameters in the low, medium, and high Mo groups were 1.0 (reference), 1.4 [95% confidence interval (CI), 0.5-3.7], and 3.5 (95% CI, 1.1-11) for sperm concentration and 1.0 (reference), 0.8 (95% CI, 0.3-1.9), and 2.6 (95% CI, 1.0-7.0) for morphology. We also found preliminary evidence for interactions between Mo and low Cu or Zn. In stratified analyses, the adjusted ORs in the high Mo/low Cu group were 14.4 (1.6, 132) and 13.7 (1.6, 114) for below-reference sperm concentration and morphology, respectively. Our findings represent the first human evidence for an inverse association between Mo and semen quality. These relationships are consistent with animal data, but additional human and mechanistic studies are needed.