Paternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
van Benthem, Jan
Bouwman, Freek G
van Schooten, Frederik Jan
MetadataShow full item record
TitlePaternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria.
Published inToxicol Sci 2018; 162(1):241-50
PubliekssamenvattingPreconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3× per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. 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 downregulated 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 downregulated, including Aldh2 and Ogg1. This discrepancy could be related to several selected microRNA (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. In conclusion, we show that paternal exposure to B[a]P can regulate mitochondrial metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers.
- Maternal intake of quercetin during gestation alters ex vivo benzo[a]pyrene metabolism and DNA adduct formation in adult offspring.
- Authors: Vanhees K, van Schooten FJ, Moonen EJ, Maas LM, van Waalwijk van Doorn-Khosrovani SB, Godschalk RW
- Issue date: 2012 Jul
- Preconceptional paternal exposure to depleted uranium: transmission of genetic damage to offspring.
- Authors: Miller AC, Stewart M, Rivas R
- Issue date: 2010 Sep
- In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective.
- Authors: Ortiz L, Nakamura B, Li X, Blumberg B, Luderer U
- Issue date: 2013 Nov 25
- Paternal benzo[a]pyrene exposure affects gene expression in the early developing mouse embryo.
- Authors: Brevik A, Lindeman B, Rusnakova V, Olsen AK, Brunborg G, Duale N
- Issue date: 2012 Sep
- Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.
- Authors: Rompala GR, Finegersh A, Homanics GE
- Issue date: 2016 Jun