A recent study sheds light on the profound impact of a father’s preconception diet on the metabolic health of their offspring, underscoring the importance of paternal lifestyle choices in shaping future generations’ well-being.
Background:
Beyond traditional Mendelian inheritance, fathers contribute to intergenerational information transfer through various mechanisms, including small non-coding RNAs (sncRNAs) present in mature spermatozoa. These sncRNAs, influenced by environmental factors, play a crucial role in embryonic development and adult phenotypes. While further research is needed to unravel the intricacies of diet-induced epigenetic changes in sperm, mounting evidence suggests their significant implications for offspring health.
Epididymal Sperm Susceptibility to Diet:
To explore how epididymal spermatozoa respond to environmental influences and discern the contributions of epididymal and spermatogenic information to paternal intergenerational effects, researchers conducted experiments on male mice. Mice were subjected to a high-fat diet (HFD) or a low-fat diet (LFD) for two weeks, followed by mating experiments to assess the impact on offspring.
Impact on Spermatogenesis and Reproductive Fitness:
Despite HFD exposure, spermatogenesis and male reproductive fitness remained unaffected. Comprehensive analyses, including testis histology and sperm motility assessments, confirmed normal spermatogenesis and minimal HFD-induced alterations.
Effects of HFD on Body Weight and Glucose Tolerance:
While HFD exposure led to a slight increase in body weight and adiposity in mice, these phenotypic changes were reversible upon returning to a regular diet. However, offspring of HFD-exposed fathers exhibited glucose intolerance, highlighting the enduring impact of paternal diet on offspring health.
Transcriptional Signatures in Offspring:
Differences in glucose tolerance among offspring were associated with unique transcriptional signatures in metabolically relevant tissues. Notably, genes linked to mitochondrial function and inflammation were differentially expressed in offspring with glucose intolerance.
Paternal Body Mass Index (BMI) and Offspring Health:
An analysis of data from the Lifestyle Intervention for Everyone (LIFE) Child Study revealed a significant correlation between paternal BMI and offspring BMI. Paternal overweight and obesity were identified as risk factors for early-onset obesity and insulin resistance in offspring.
Role of mt-tRNAs:
Mitochondrial transfer sncRNAs (mt-tRNAs) were found to be upregulated in response to HFD exposure, suggesting their role in mediating paternal epigenetic effects. Human studies further supported the association between mt-tRNAs and metabolic parameters.
Mitochondrial Dysfunction Mimics HFD Effects:
Transcriptomic analyses revealed downregulation of genes involved in mitochondrial metabolism in diet-exposed mice, coupled with compensatory upregulation of mtDNA transcriptional machinery in spermatozoa. These findings suggest a direct link between paternal diet-induced mitochondrial dysfunction and offspring metabolic disorders.
Conclusions:
In summary, the study underscores the significant impact of paternal diet on offspring metabolic health, mediated by mitochondrial signals transmitted through spermatozoa. While the study highlights the potential of mt-tRNAs as biomarkers for monitoring preconception lifestyle interventions, further research is warranted to elucidate the broader implications of paternal metabolic health on offspring well-being.