Paternal Malnutrition has Organ-Specific Intergenerational Effects on Mitochondrial Function and Oxidative Stress
Esther S Lenssen1, Sonia de Assis2, Alex Remels1
1Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands, The Netherlands.
Abstract:
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.
Insights
Paternal malnutrition before conception impacts offspring
Area of Science:
- Epigenetics and developmental biology
- Maternal and paternal health
- Oxidative stress and DNA damage research
Background:
- Paternal pre-conceptional lifestyle factors can influence offspring health.
- The impact of paternal malnutrition on offspring's mitochondrial function and DNA damage requires further investigation.
Purpose of the Study:
- To investigate the effects of paternal low protein diet (LPD) on mitochondrial function, oxidative stress, and DNA damage in adult mouse offspring.
- To determine if these effects are tissue-specific in lung and liver.
Main Methods:
- Male mice were fed control or LPD diets pre-conceptionally.
- Offspring were maintained on control diets until adulthood.
- Mitochondrial DNA copy number, citrate synthase activity, gene expression, and 8-oxo-deoxyguanosine (8-oxo-dG) levels were analyzed in offspring lung and liver tissues.
Main Results:
- Paternal LPD increased mitochondrial copy number and citrate synthase activity in offspring lung and liver.
- Gene expression related to mitochondrial biogenesis decreased in offspring lungs but not livers.
- Oxidative DNA damage (8-oxo-dG) increased in offspring lungs but decreased in livers, correlating with antioxidant enzyme expression.
Conclusions:
- Pre-conceptional paternal malnutrition induces tissue-specific alterations in mitochondrial function and DNA damage in offspring.
- These findings highlight the role of paternal nutrition in developmental programming and long-term offspring health.
