Humans are exposed occupationally and environmentally to metal aerosols including lead (Pb2+) and cadmium (Cd2+). These toxicants accumulate in male reproductive organs. Epidemiological studies have been equivocal about effects of Pb2+ and Cd2+ on hormone concentrations, male fertility and sperm parameters. Comparison of Pb2+ and Cd2+ concentrations in fertile and infertile men are problematic. Problem areas include failure to control confounding variables, but genetic polymorphisms as in somatic diseases may modulate Pb2+ and Cd2+ damage. Multiple calcium (Ca2+) and potassium (K+) channel isoforms have been identified in human testes and spermatozoa. These Ca2+ and K+ channels are involved in early events of acrosome reactions. Ca2+ channel are susceptible to Cd2+ poisoning and K+ channels to Pb2+. These channels offer entry paths for metallic toxicants into mature spermatozoa. Ion channel polymorphisms may cause differential sensitivities to Cd2+ and Pb2+, explaining in part prospective blinded studies showing high Cd2+ in varicocele-related human infertility and high Pb2+ in unexplained infertility. In both forms of male infertility the ability to undergo an acrosome reaction decreases. Reverse transcriptase-polymerase chain reaction assays for Ca2+ and K+ channel isoforms may identify susceptibility subgroups with lower resistance to environmental exposures.

Initial sperm-egg binding in mammals involves recognition of glycosylated proteins of egg zonae by glycosylated proteins on sperm surfaces. Egg zona protein structure is relatively simple, and has been strongly conserved. Species specificity must reside in the carbohydrate modifications on the egg surface, and in the co-ordinated assembly of a unique cohort of sperm proteins at capacitation. Fruitful advances have been made along four lines. Oligosaccharide structures capable of binding spermatozoa have been dissected by in-vitro synthesis and binding experiments, informed by the general advance of knowledge of protein glycosylation processes. Site-specific mutagenesis of zona proteins and their expression in tissue culture have identified glycosylation sites involved in species-specific sperm binding. Antibody and lectin labelling studies show a continuing process of remodeling of glycosylated sperm surface epitopes within a set of stable compartments during epididymal transit and capacitation of spermatozoa. Characterization of sperm-egg binding proteins from a variety of mammalian species shows that a different set of effectors induce acrosome reactions in each species, with each set including one or more sugar-recognizing proteins. Sequencing of some of these effectors suggests that each group may form a supermolecular complex to induce a species-specific acrosome reaction, with the functional activities distributed in a species limited or non-limited manner among the individual proteins.

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To investigate a possible common environmental exposure that may partially explain the observed decrease in human semen quality, we correlated seminal plasma and blood cadmium levels with sperm concentration and sperm motility. We studied three separate human populations: group 1, infertility patients (Long Island, NY, USA); group 2, artificial insemination donors (AID) (Rochester, NY, USA); and group 3, general population volunteers (Rochester, NY, USA). Information about confounding factors was collected by questionnaire. Seminal plasma cadmium did not correlate with blood cadmium (Spearman correlation, n = 91, r = -0.092, P = 0.386, NS). Both blood and seminal plasma cadmium were significantly higher among infertility patients than the other subjects studied (for example, median seminal plasma cadmium was 0.282 μg/L in infertility patients versus 0.091 μg/L in AID and 0.092 μg/L in general population volunteers; Kruskal-Wallis test, P < 0.001). The percentage of motile sperm and sperm concentration correlated inversely with seminal plasma cadmium among the infertility patients (r = -0.201, P < 0.036 and r = -0.189, P < 0.05, respectively), but not in the other two groups. Age (among infertility patients) was the only positive confounder correlating with seminal plasma cadmium. To validate our human findings in an animal model, we chronically exposed adolescent male Wistar rats to low-moderate cadmium in drinking water. Though otherwise healthy, the rats exhibited decreases in epididymal sperm count and sperm motility associated with cadmium dose and time of exposure. Our human and rat study results are consistent with the hypothesis that environmental cadmium exposures may contribute significantly to reduced human male sperm concentration and sperm motility.