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.

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Abstract. Equine protozoal myeloencephalitis (EPM) is a neurological disease of horses and ponies caused by the apicomplexan protozoan parasite Sarcocystis neurona. The purposes of this study were to develop the most stringent criteria possible for a positive test result, to estimate the sensitivity and specificity of the EPM Western blot antibody test, and to assess the ability of bovine antibodies to Sarcocystis cruzi to act as a blocking agent to minimize false-positive results in the western blot test for S. neurona. Sarcocystis neurona merozoites harvested from equine dermal cell culture were heat denatured, and the proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in a 12-20% linear gradient gel. Separated proteins were electrophoretically transferred to polyvinylidene fluoride membranes and blocked in 1% bovine serum albumin and 0.5% Tween-Tris-buffered saline. Serum samples from 6 horses with S. neurona infections (confirmed by culture from neural tissue) and 57 horses without infections (horses from the Eastern Hemisphere, where S. neurona does not exist) were tested by Western blot. Horses from both groups had reactivity to the 62-, 30-, 16-, 13-, 11-, 10.5-, and 10-kD bands. Testing was repeated with another step. Blots were treated with bovine S. cruzi antibodies prior to loading the equine samples. After this modification of the Western blot test, positive infection status was significantly associated with reactivity to the 30-and 16-kD bands (P Ͻ 0.001, Fisher's exact test). The S. cruzi antibody-blocked Western blot had a sample sensitivity of 100% and sample specificity of 98%. It is concluded that the specificity of the Western blot test is improved by blocking proteins not specific to S. neurona and using reactivity to the 30-and 16-kD bands as the criterion for a positive test.