Paternal effects of lead in the F(1) and F(2) generations of rats: Hippocampal morphology and embryofetal protein synthesis.

Abstract

The potential for heritable effects of toxicants on development and reproduction via paternal exposure has not been well studied. This study will examine reproductive outcomes in the F{dollar}\sb0{dollar} lead-treated, and F{dollar}\sb1{dollar} males and females from paternal exposure Sprague-Dawley rats. Outcomes assessed were fertility and litter size in freely breeding pairs and progression of superovulated oocytes to 2-cell embryos. Protein synthesis in 2-cell embryos and hippocampal cultures of post-natal day 1 (PN1) offspring was monitored by {dollar}\sp{lcub}35{rcub}{dollar}S-methionine incorporation and 2-dimensional gel electrophoresis. Reproductive tissue lead levels in the F{dollar}\sb0{dollar} were measured using graphite furnace atomic absorption spectrometry. F{dollar}\sb0{dollar} males with B-Pb levels in the range 29-60 {dollar}\mu{dollar}g/dL showed a reduction in breeding success (measured by breeding pairs producing litters), without a reduction in the mean litter size. Lower dosed animals did not show indications of fertility effects. Male and female offspring (F{dollar}\sb1{dollar}) of the high dose animals (F{dollar}\sb0{dollar}) were assessed by natural breeding, superovulation and hippocampal cultures for indications heritable effects of paternal lead exposure. Reductions in both breeding success and mean litter size were observed in F{dollar}\sb1{dollar} males. Effects in F{dollar}\sb1{dollar} females appear to be in breeding success, but litter size could not be adequately determined due to small sample size. Alterations in protein synthesis in the F{dollar}\sb1{dollar} 2-cell embryos were observed as a dose related increase in protein synthesis of the major protein product which is associated with the initial expression of the embryonic genome. F{dollar}\sb1{dollar} 2-cell embryo results indicate male-mediated effects of lead may be observed immediately following the switch from maternal to embryonic control of protein synthesis. Alterations in protein synthesis in F{dollar}\sb1{dollar} and F{dollar}\sb2{dollar} hippocampal cultures are indications of heritable effects of paternal lead exposure. The paternally mediated effects observed in 2-cell embryos and hippocampal cultures may result from more than one effect of lead. It is possible that effects observed in F{dollar}\sb1{dollar} 2-cell embryos are of a regulatory nature, while F{dollar}\sb2{dollar} hippocampal alterations are genetically linked.