A review in Clinical Epigenetics synthesizes growing evidence that paternal lifestyle and environmental exposures such as diet, obesity, smoking, endocrine-disrupting chemicals, and stress alter sperm epigenetic marks (DNA methylation, histone retention, and small non-coding RNAs). These changes can influence sperm quality and fertilizing ability, early embryo development, assisted reproduction outcomes, and long-term health risks in offspring.

Key findings include:

• Paternal factors leave epigenetic “signatures” in sperm (DNA methylation, histone modifications, sncRNAs) that accompany the genome at fertilization.
• Obesity and diet (high-fat/high-sugar or folate deficiency) are linked to altered methylation and sncRNA profiles, impaired sperm parameters, and metabolic dysfunction in offspring.
• Smoking associates with differentially methylated regions in genes tied to anti-oxidation, insulin signaling, and spermatogenesis, and with reduced motility/morphology.
• Endocrine-disrupting chemicals (EDCs) (e.g., BPA, phthalates) can induce transgenerational DNA methylation changes, affecting fertility and disease risk.
• Stress in fathers before conception correlates with altered sperm miRNAs/piRNAs and methylation, with behavioral and metabolic effects detected across generations in animal models.
• ART implications: Male BMI, diet, and alcohol intake correlate with embryo quality and ICSI outcomes; epigenetic sperm profiles show promise as biomarkers to improve ART success.
• Clinical takeaway: Preconception interventions weight management, smoking cessation, balanced diet (including folate), physical activity, and reduced toxin exposure may help reverse adverse sperm epigenetic marks.

While maternal epigenetics is well studied, this review highlights mounting evidence for paternal epigenetic influences, notes confounders (genetic background, fluctuating behaviors), and calls for longitudinal, controlled human studies using modern methylation and RNA-sequencing platforms.

Male preconception health is a modifiable lever for improving fertility, embryo viability, and the lifelong health trajectory of children. Incorporating epigenetic screening or lifestyle programs into fertility care could enhance ART outcomes and reduce intergenerational disease risk.

Next steps include:

• Large, longitudinal human cohorts to establish causality and dose–response.
• Standardized epigenome assays (e.g., MethylationEPIC, small-RNA profiling) in andrology/ART workflows.
• Trials testing preconception lifestyle interventions on sperm epigenetic readouts and clinical endpoints.

Practical guidance include:

• Maintain healthy weight; prioritize balanced diet with adequate folate.
• Avoid smoking, excessive alcohol, and high-fat/high-sugar patterns.
• Reduce exposure to EDCs (e.g., minimize plastics/heat, check workplace risks).
• Manage stress; support sleep and physical activity.
• Discuss preconception health with fertility specialists; consider participation in studies monitoring sperm epigenetic markers.

Provided by
Nazarbayev University