Paternal Malnutrition has Organ‐Specific Intergenerational Effects on Mitochondrial Function and Oxidative Stress Induced DNA Damage in Male Mouse Offspring

Paternal pre-conceptional lifestyle may affect the offspring's levels of oxidative DNA damage. Therefore, we investigated whether paternal malnutrition affected mitochondrial function, oxidative stress, and DNA damage in lung and liver of mouse offspring at adult age. Adult male C57Bl6 mice received a control or low protein diet (LPD) and were mated with female mice reared on control diets. Offspring was kept under control feeding conditions until adult age. Compared to control, mitochondrial copy number and citrate synthase activity were higher in lung and liver of offspring whose fathers received LPD. Moreover, expression of genes involved in mitochondrial biogenesis was lower in lungs of offspring whose fathers received LPD, but no changes were observed in liver. Mitochondria may be a source of oxidative stress and indeed, levels of 8-oxo-deoxyguanosine (8-oxo-dG) were higher in lungs of offspring whose fathers received LPD. On the contrary, 8-oxo-dG levels in liver were lower in offspring whose father received LPD, which was associated with the tissue-specific expression of enzymatic antioxidants catalase, NAD(P)H: quinone oxidoreductase 1 and γ-glutamylcysteine synthetase. This study confirms that pre-conceptional paternal malnutrition can influence background levels of DNA damage and mitochondrial function in a tissue-specific manner in offspring.