Review reveals how paternal lifestyle shapes sperm epigenetics and offspring health

A new review in Clinical Epigenetics synthesises 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 fertilising ability, early embryo development, assisted reproduction outcomes, and long-term health risks in offspring.

Key findings

  • Paternal factors leave epigenetic "signatures" in sperm (DNA methylation, histone modifications, sncRNAs) that accompany the genome at fertilisation.

  • 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 signalling, 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 behavioural 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.

Research context

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

Why it matters

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

Next steps

  • Large, longitudinal human cohorts to establish causality and dose-response.

  • Standardised 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

  • Maintain healthy weight; prioritise balanced diet with adequate folate.

  • Avoid smoking, excessive alcohol, and high-fat/high-sugar patterns.

  • Reduce exposure to EDCs (e.g., minimise 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.

Source:
Journal reference:

Akhatova, A., et al. (2025). How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health. Clinical Epigenetics. doi.org/10.1186/s13148-025-01815-1

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