Animal models are important for predicting human reproductive and developmental toxicity (Tyl 2005; Cooper and Doerrer 2010; Daston and Knudsen 201), but, because of differences in such things as pharmacokinetics and hormonal regulaton of parturition, their validity in modeling human pathologic conditions (in particular, conditions that are of a complex and multifactorial nature, such as preterm birth) must be considered in interpreting the data. The use of animal studies for lead risk assessment has important limitations. For example, human spermatogenesis is far less efficient than that of other mammals, with efficiency being defined as the estimated number of spermatozoa generated per day per gram of testicular parenchyma (Amann 1970; Johnson 1995; Johnson et al. 2000). Teratozoospermia (abnormal sperm morphology) is more common in humans than in animal models (Hafez 1987; WHO 2010).Although it remains unclear what animal species or strain is best for modeling lead effects on humans, the only consistent findings on the effects of lead exposure in the male animal and the human male are related to decreased sperm motility and increased spontaneous acrosome loss. Thus, one could infer that lead exposure may have a more deleterious effect on sperm function than on sperm production, and thus affect male fertility status, than previously thought.
Male Reproductive Effects
The committee considered two broad types of human epidemiologic studies during its deliberations: occupational studies and studies of male patients in infertility clinics. In general, the committee focused its review on studies in which BLLs were reported. It also considered studies in which lead concentrations in seminal fluid (total ejaculate, including fluids produced by the accessory sex glands—seminal vesicles and prostate—and sperm) or seminal plasma (fluid remaining after sperm are removed from the ejaculate) were measured.
Several studies report an association between occupational lead exposure and decreased sperm count, velocity, and motility; greater haploidy of sperm DNA; and morphologically apparent sperm abnormalities. The studies were of men who worked in battery- or paint-manufacturing plants for 10-15 years. Workers in the highest-exposure groups had mean BLLs of 68.26 μg/dL (Naha and Manna 2007) and 77.22 μg/dL (Naha and Chowdhury 2006). Nonoccupationally exposed controls had mean BLLs of 10-15 μg/dL. A Taiwanese study reported that male lead-battery workers who had BLLs of 45 μg/dL or over had more sperm head abnormalities, greater sperm DNA denaturation, and greater sensitivity to denaturation than workers who had BLLs under 25 μg/dL (Hsu et al. 2009). In contrast, no association was observed between lead exposure and changes in semen volume; sperm count, motility, or velocity; or ROS production in the same study. Kasperczyk et al. (2008) reported that Polish metalworkers who had a mean BLL of 53.1 μg/dL had lower sperm motility and higher seminal