BackgroundEvidence 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.ObjectivesOur goal in this study was to assess relationships between exposure to multiple metals at environmental levels and human semen-quality parameters.MethodsWe 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.ResultsAmong 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.ConclusionsOur 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.

Study Objective To explore associations between exposure to metals and male reproductive hormone levels. Design Cross-sectional epidemiology study with adjustment for potential confounders. Setting Metal concentrations and reproductive hormone levels were measured in blood samples collected from 219 men. Patients: Men recruited through two Michigan, USA infertility clinics. Interventions None Main Outcome Measures Serum FSH, LH, inhibin B, testosterone, and SHBG. Results Cadmium, copper and lead were all significantly or suggestively positively associated with testosterone when modeled individually (p-values = 0.1, 0.03, and 0.07, respectively), findings that are consistent with limited previous human and animal studies. Conversely, molybdenum was associated with reduced testosterone (p-value for trend = 0.001). A significant inverse trend between molybdenum and testosterone remained when additionally considering other metals in the model, where a positive association between testosterone and zinc was also found. Finally, in exploratory analysis there was evidence for an interaction between molybdenum and zinc, where high molybdenum was associated with a 37% reduction in testosterone (relative to the population median level) among men with low zinc. Conclusions While reductions in testosterone and reproductive toxicity following molybdenum exposure have been previously demonstrated in animal studies, more research is needed to determine whether molybdenum poses a risk to human reproductive health.

Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decreases in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.

Phthalates are ubiquitous industrial chemicals that are reported to adversely affect human reproductive outcomes. Divergent effects on semen quality have been reported in a limited number of studies. To assess the possible contribution of regional differences in phthalate exposure to these results, we wished to determine if ambient phthalate exposure of men from the Great Lakes region was associated with human sperm parameters. Male partners (N=45) of subfertile couples presenting to a Michigan infertility clinic were recruited. Urinary concentrations of several phthalate metabolites were measured in these men. Semen parameters, measured according to the World Health Organization [WHO 1999] protocols, were divided into those at or above WHO cutoffs for motility (50% motile), concentration (20 million/mL) and morphology (4% normal) and those below. Phthalate metabolite concentrations were divided into those concentrations above the median and those at or below the median. Specific gravity was used as a covariate in the regression models to adjust for urine dilution. Low sperm concentration was significantly associated with above median concentrations of monoethyl phthalate (MEP) (OR=6.5, 95% CI: 1.0-43.6) and low morphology with above median concentrations of mono-3-carboxypropyl phthalate (OR=7.6, 95% CI: 1.7-33.3). Increased odds for low concentration and above median concentrations of metabolites of di(2-ethylhexyl) phthalate (DEHP) (OR=5.4, 95% CI: 0.9-30.8) and low morphology and above median concentrations of MEP (OR=3.4, 95% CI: 0.9-13.8) were also found. A significant trend was observed for tertiles of MEP and low sperm concentration (p=0.05). Results suggest that ambient phthalate metabolite concentrations may adversely affect human semen quality.