Sex dependent intergenerational effects of lead in mouse model

Abstract

Lead (Pb) exposure negatively impacts fertility in both males and females, pregnancy outcomes, and child brain development. We investigated the reproductive and neurological effects of Pb exposure on male and female mice via Pb-contaminated soil for 4 weeks. Breeding was conducted after completion of exposure, in four groups; group 1 consisted of exposed dams and unexposed sires, group 2 consisted of exposed sires and unexposed dams, group 3 consisted of exposed sires and exposed dams and group 4 was the control. Generally, Pb exposure reduced observed conception rates, with a cumulative decrement observed when both males and females are exposed. Gene expression of the testes revealed oxidative stress as the cause of reduced conception rates. Neurological tests: Morris water maze and rotarod were conducted on F1 generation offspring. Maternally and paternally exposed F1 mice performed poorly in the Morris water maze when compared to the control. The severity of the neurological effects was also parent-dependent and sex-dependent. Paternal Pb exposure effects were more pronounced in female offspring. A comparison of gene expression changes of the hippocampus and prefrontal cortex showed paternal Pb-exposure resulted in more prefrontal cortex changes than in the hippocampus, a trend also recorded in the exposed sires. The pronounced effects in female offspring of paternal Pb exposure may suggest that Pb neurological effects may be X-chromosome-linked.