| Cadmium, Lead, and Other Metals in Relation to Semen Quality: Human Evidence for Molybdenum as a Male Reproductive Toxicant John D. Meeker,1 Mary G. Rossano,2 Bridget Protas,3 Michael P. Diamond,4 Elizabeth Puscheck,4 Douglas Daly,5 Nigel Paneth,3 and Julia J. Wirth3 1Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA; 2Department of Animal and Food Sciences, University of Kentucky, Lexington, Kentucky, USA; 3Department of Epidemiology, Michigan State University, East Lansing, Michigan, USA; 4Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA; 5Grand Rapids Fertility and IVF, Grand Rapids, Michigan, USA Abstract
Background: 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. Objectives: Our goal in this study was to assess relationships between exposure to multiple metals at environmental levels and human semen-quality parameters. Methods: 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. Results: 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. Conclusions: 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. Key words: biomarkers, epidemiology, exposure, fertility, metals, sperm. Environ Health Perspect 116: 1473–1479 (2008) . doi:10.1289/ehp.11490 available via http://dx.doi.org/ [Online 1 July 2008]
Address correspondence to J. Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S. Observatory St., Ann Arbor, MI 48109 USA. Telephone: (734) 764-7184. Fax: (734) 936-7283. E-mail: meekerj@umich.edu This work was supported by grant ES11856 from the National Institute of Environmental Health Sciences, National Institutes of Health. J.D.M. is supported by a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute. The authors declare they have no competing financial interests. Received 18 March 2008 ; accepted 1 July 2008.
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