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

      Gandley, Robin Elizabeth; Silbergeld, Ellen K. (1993)
      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.