father's

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Can a father’s lifestyle choices before conception influence the health of his future children? New research ¹ reveals that environmental factors affecting fathers can leave molecular footprints in embryos, shaping development and potentially impacting long-term health.

Epigenetic inheritance

For decades, scientists believed that inheritance was controlled exclusively by DNA sequences passed from parents to offspring. Today, researchers recognize the critical importance of epigenetic inheritance, the transmission of biological traits through chemical modifications to DNA and its associated proteins. These modifications don’t change the genetic code itself but control how genes are activated or silenced, often in response to environmental factors such as stress, diet, or medication exposure.

While maternal epigenetic inheritance seems intuitive given the direct biological connection between mother and developing embryo during pregnancy, emerging research demonstrates that fathers can also transmit environmentally induced epigenetic changes to their children. However, how common this phenomenon is and the mechanisms driving it have remained largely mysterious.

Paternal influence

This comprehensive study examined how specific paternal environmental conditions affect early embryonic development in mice under carefully controlled genetic and environmental conditions. To create environmental perturbations, prospective mouse fathers were exposed to either antibiotics that disrupted their gut microbiome or a low-protein, high-sugar diet. Using in vitro fertilization to minimize experimental variability, researchers collected embryos approximately four days after fertilization and analyzed each individually to measure differences in gene expression compared to control embryos from untreated fathers.

Both environmental perturbations caused significant changes in embryonic gene expression. To understand how genetic background influences these effects, scientists repeated experiments using a different mouse strain, the equivalent to a different mouse race. The results they obtained differed, suggesting a complex interplay between genetics and environment in inheritance.

Paternal age was a factor that also resulted in changes. Embryos derived from older fathers showed stronger effects on gene expression, particularly in genes involved in immunity. This indicates that paternal age, and not only maternal one, has effects on the offspring.

Personalized approaches

The findings challenge traditional views of inheritance and suggest that a father’s preconception health and environmental exposures may have more profound effects on offspring than previously recognized. The long held view that only maternal age affected (negatively) the embryos needs to be updated to include paternal influence. Understanding how epigenetic influences (from both parents) influence embryonic development could inform clinical recommendations and contribute to personalized approaches to family planning and disease prevention. Already the finding that paternal health status –and age– influence the unborn embryo has potential to revolutionise our current understanding of the role of each parent in their offspring.

References

Leonard C. Steg, Isabelle M. Mansuy (2025) A father’s legacy: the sperm epigenome, preimplantation development, and paternal environment Epigenomics doi: 10.1080/17501911.2025.2569301 ↩

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