Paternal Diet and Epigenetic Inheritance: Unveiling Nutritional Influences on Offspring Metabolic Programming

Emerging evidence highlights the critical role of paternal nutrition in shaping the metabolic health of offspring through epigenetic inheritance mechanisms. This review synthesizes recent advances (2015 to 2025) in understanding how paternal dietary patterns before conception modulate the sperm epigenome and influence transgenerational metabolic programming. Central to this process are dynamic alterations in DNA methylation, histone modifications, and Noncoding RNAs (ncRNAs), which serve as molecular carriers of environmental information from father to offspring. High-fat or protein-restricted paternal diets have been consistently associated with aberrant methylation of key metabolic genes, shifts in histone acetylation and methylation, and changes in sperm-borne miRNAs, collectively predisposing offspring to obesity, insulin resistance, and glucose intolerance. Advanced molecular tools, including bisulfite sequencing, ChIP-seq, and RNA-seq, have enabled precise profiling of these heritable epigenetic signatures. The review also examines experimental and human epidemiological studies that confirm the persistence of these effects into adulthood, reinforcing the long-term implications of paternal nutritional status. Importantly, emerging strategies such as nutritional supplementation, CRISPR-based epigenome editing, and personalized preconception dietary interventions offer promising avenues to mitigate adverse transgenerational outcomes. Furthermore, the review explores novel biochemical mediators, microplastics, gut-derived metabolites, circadian disruptions, and phytochemicals that interact with sperm epigenetics and highlights the future potential of artificial intelligence in predicting epigenetic inheritance patterns. By integrating molecular, epidemiological, and computational insights, this review underscores the underrecognized yet profound influence of paternal diet on offspring health and advocates for the inclusion of paternal nutrition in public health discourse and preventive strategies. Addressing this gap is imperative for curbing the intergenerational transmission of metabolic disorders and promoting lifelong health across generations.