Paternal exposure to environmental chemical stress affects male offspring’s hepatic mitochondria
The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age. Analysis of the liver proteome by 2D-gel electrophoresis and mass spectrometry indicated that proteins involved in mitochondrial function were significantly down-regulated in the offspring of exposed fathers.
This down-regulation of mitochondrial proteins was paralleled by a reduction in mitochondrial DNA copy number and reduced activity of citrate synthase and β−hydroxyacyl-CoA dehydrogenase, but in male offspring only.
Surprisingly, analysis of hepatic mRNA expression revealed a male-specific up-regulation of the genes, whose proteins were down-regulated, including Aldh2 and Ogg1. This discrepancy could be related to several selected miRNA’s that regulate the translation of these proteins; miRNA-122, miRNA-129-2-5p and miRNA-1941 were upregulated in a gender-specific manner.
Since mitochondria are thought to be a source of intracellular reactive oxygen species, we additionally assessed oxidatively-induced DNA damage. Both 8-hydroxy-deoxyguanosine and malondialdehyde-dG adduct levels were significantly reduced in male offspring of exposed fathers.