lipid peroxidation than nonexposed office workers who had a mean BLL of 8.47 μg/dL. The authors also reported no difference in semen volume, sperm count, or sperm morphology among or between the groups. One problem associated with these occupational studies is that many of the control groups were reported to have BLLs over 8 μg/dL, so it was difficult to assess the effects of very low lead exposures and to determine whether there actually is a “safe” level of lead exposure. That may help to explain why epidemiologic studies have produced conflicting findings.
Several studies have examined men who were exposed to lead nonoccupationally. In general, BLLs of nonexposed, nonsmoking subjects recruited from the general population or from infertility clinics were generally lower than those seen in the occupational studies. BLLs (up to about 15 μg/dL) in Croatian men without occupational exposure to lead or other metals were associated with increased percentages of pathologic sperm, including wide sperm and round sperm (Telisman et al. 2007). Chia et al. (1992) reported that men who were attending an andrology clinic in Singapore and had reduced sperm motility had higher BLLs (mean 7.2 μg/dL) than men who had normal sperm motility (mean 5.1 μg/dL). However, blood cadmium concentration was also increased in this study population (Chia et al. 1992). Other studies of men who were attending infertility clinics reported no association between BLL (mean 8-15 μg/dL) and alterations in sperm characteristics (Xu et al. 1993; Meeker et al. 2008; Mendiola et al. 2011). The largely negative studies may reflect in part the use of sperm counts as the primary indicator of lead-associated infertility effects. There is strong evidence that human sperm count displays geographic, regional, and time-dependent decreases (Carlsen et al. 1992; Swan 2006). Spermatogenesis is testosterone-dependent. Consistent with the reports of declining sperm counts, Travison et al. (2007) reported that serum testosterone is declining over calendar time (for example, in birth cohorts) in American men and that the decline is age-independent. Therefore, serum hormone concentrations are also inappropriate as biomarkers of the potential antireproductive effects of lead in the human male. Another weakness of the studies is the failure to control for untreated fertility issues in the female partners of the study subjects and for the effects of other metal contaminants.
Several relatively recent investigations have focused on semen lead concentration as a biomarker, as has long been the case in the reproduction community (see review by Benoff et al. 2000). Mendiola et al. (2011) reported an association between semen lead concentration and increased percentage of immotile sperm; however, the analysis failed to adjust for exposure to other metals. Slivkova et al. (2009) reported a negative correlation between semen lead concentration and pathologic changes in sperm (specifically, flagellum ball), but no correlations with other sperm alterations were observed. There is additional evidence that increasing seminal plasma lead concentrations are associated with alterations in two sperm functions required for fertilization: decreased motility, which is the major determinant of pregnancy outcome (Shulman et al. 1998; Stone et al. 1999), and increased spontaneous acrosome loss (Benoff et al. 2000, 2003a,b). The latter process can be mimicked by incubating fertile donor sperm in medium containing lead at levels seen in seminal plasma (Benoff et al. 2000,