Sex Dependent Intergenerational Effects of Lead in Mouse Model

Abstract

Lead contaminated soils remains one of the major sources of lead (Pb) exposure with high impact on fertility in both males and females, pregnancy outcomes and child brain development. We investigated inhalation and ingestion as medium of Pb exposure via soil in male and female mice. Exposure was then withdrawn prior to mating thus we investigated the lingering effects of Pb on fertility in F0 generation and neurological development in F1 generation. Lead exposure reduced conception rates with a cumulative decrement being recorded when both males and females are exposed. Male testicular gene expression revealed reduction in fertility was caused by oxidative stress. Cessation of exposure did not alleviate neurological deficits in F1 generation, as offspring of exposed individuals performed poorly in the water Morris test when compared to control. The severity of the effects was also parent dependent and sex dependent. Paternal Pb exposure also caused some neurological and motor deficits, with effects being more pronounced in female offspring. The female offspring of paternal Pb exposure showed gene expression of changes occurring more in prefrontal cortex than in hippocampus, a trend recorded in their sires. This trend suggests that Pb neurological effects may be X- chromosome linked.