Lead toxicity and the hypothalamic-pituitary-testicular axis

Abstract

Environmental exposure to toxic levels of lead occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. Clinical and animal studies indicate that abnormalities of spermatogenesis result from toxic lead exposure, but the pathogenetic mechanisms involved have not been identified. In order to ascertain what reproductive abnormalities occur in experimental animals when exposed to low levels of lead, 52-day-old animals were treated with water containing 0.0% (control), 0.1%, or 0.3% lead acetate for 30 days prior to killing. Whole blood serum lead levels were below detection (<7 μg/dl) in the control animals, 34 ± 3 μg/dl in the 0.1% group, and 60 ± 4 μg/dl in the 0.3% group (P<0.001). Significant negative correlations between whole blood lead levels and serum and intratesticular testosterone values were found (r=0.64, P<0.001 and r=0.6, P<0.001, respectively). As the level of lead exposure increased, intratesticular sperm counts significantly decreased (r=0.81, P<0.001). No significant changes in serum luteinizing hormone (LH) values were found, but sperm follicle-stimulating hormone (FSH) values were significantly suppressed (P<0.05) after lead treatment. There was a significant decrease in ventral prostate weight (P<0.05), but no differences in testicular or seminal vesicle weights. Our data indicate that dietary exposure to lead resulting in whole blood serum lead values considered acceptable in the workplace (≤40 μg/dl) causes inhibition of testicular function. The failure to demonstrate elevated LH and FSH values in the face of markedly decreased serum testosterone and ventral prostate weight values suggests either a predominant mechanism of action of lead toxicity at the level of the hypothalamic-pituitary axis or a combined defect involving the gonad and hypothalamic-pituitary sites.