Male reproductive toxicity of lead in animals and humans. ASCLEPIOS Study Group.

Abstract

Objective-To critically review the literature on male reproductive toxicity of lead in animals and humans. Methods-A systematic literature search identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents. The studies were evaluated by paying attention mainly to sample size, study design, exposure, and dose characterisation, analytical method standardisation, and quality assurance. Results-Several studies on rats and other rodents indicated that blood lead concentrations >30-40 µg/dl were associated with impairment of spermatogenesis and reduced concentrations of androgens. However, other animal studies, mainly about histopathological, spermatozoal, and hormonal end points, indicated that certain species and strains were quite resistant to the reproductive toxicity of lead and that diVerent testicular lead concentrations could account for these diVerences. The human studies focused mainly on semen quality, endocrine function, and birth rates in occupationally exposed subjects, and showed that exposure to concentrations of inorganic lead >40 µg/dl in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology. No relevant eVects were detected on endocrine profile. Conclusion-Several factors make it diYcult to extrapolate the animal data to the human situation. The diYculties are mainly due to diVerences between species in reproductive end points and to the level of exposure. Concentrations of blood lead >40 µg/dl seemed to be associated with a decrease in sperm count, volume, motility, and morphological alterations and a possible modest eVect on endocrine profile. Dose-response relation, in particular at a threshold level, is poorly understood, and site, mode, or mechanism of action are unknown. Also, the eVects were not always the same or associated in the same way, although the prevalent eVects were on sperm count and concentration. Some methodological issues and indications for future studies are discussed. (Occup Environ Med 1998;55:364-374)

Understanding the human health effects of chemical mixtures.

“…Lead also functions as an endocrine disruptor, causing reduced sperm count, reduced semen volume, and changes in sperm motility and morphology [for a review, see Apostoli et al (58)]. Male lead exposure has been associated with increased infertility (59).…”

Lead induced alterations in rabbit spermatozoa motility and morphology in vitro

“…Studies in rats and other rodents showed that Pb is associated with impaired spermatogenesis and reduction in the level of androgens (Wang et al 2008(Wang et al , 2013Pandya et al 2012). Reproductive studies primarily focused on male semen quality, endocrine function, and fertility in labour-exposed individuals, which showed that exposure to a concentration > 40 mg/dl inorganic Pb resulted in decreased spermatozoa count, ejaculate volume and density, motility, and a change of the morphology of spermatozoa (Apostoli et al 1998). No significant effects on endocrine functions have been identified (Apostoli et al 1998).…”

“…Reproductive studies primarily focused on male semen quality, endocrine function, and fertility in labour-exposed individuals, which showed that exposure to a concentration > 40 mg/dl inorganic Pb resulted in decreased spermatozoa count, ejaculate volume and density, motility, and a change of the morphology of spermatozoa (Apostoli et al 1998). No significant effects on endocrine functions have been identified (Apostoli et al 1998). Similarly, lead acetate administered to older male rabbits subcutaneously at a dose range of 0 to 3.85 mg/kg 3 times a week caused an adverse change in the number of spermatozoa in ejaculate volume, the percentage of motile spermatozoa, the speed of movement of spermatozoa, and spermatozoa morphology after 5 weeks of exposure (Moorman et al 1998).…”

Lead Exposure and Environmental Health

“…A systematic literature search in the effect of lead on reproductive toxicity identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents (Apostoli et al, 1998). Nevertheless, metals occur as mixtures in the environment and risk assessment procedures for metals currently lack a framework to incorporate chronic metal mixture toxicity (Nys et al, 2015).…”