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Parental exercise mediates fetal metabolic and cardiac programming

Nature Reviews Endocrinology (2025)Cite this article

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Abstract

The role of physical activity and exercise training in preventing the development of chronic disease and reducing mortality is increasingly recognized. A substantial body of evidence indicates that exercise confers these benefits to subsequent generations. This Review examines the effects of parental exercise, focusing on findings published within the past 10 years and related to mechanisms of transmission and sex-specific differences in both parents and offspring. Epigenetic modifications, including DNA methylation, histone modification and small non-coding RNAs, are crucial in how parental exercise influences offspring development. Paternal exercise alters the small RNA pool and methylation profiles in sperm, whereas maternal exercise affects both the in utero environment and postnatal lactation factors. Notably, male offspring show enhanced metabolic benefits, whereas female offspring exhibit greater cardiac improvements than male offspring. These findings highlight the sex-dependent nature of the generational effects of exercise and emphasize the need for further research into the molecular underpinnings and long-term implications for both male and female offspring.

Key points

  • Over the past decade, maternal and paternal exercise have emerged as tools to prevent the increasing prevalence of cardiac and metabolic disease in offspring.

  • A number of studies investigating parental exercise have improved understanding of its tissue-specific and sex-specific effects on offspring.

  • Studies have shown that beneficial effects of parental exercise extend to the second-generation offspring (F2) of dams that exercised in the founding generation (F0).

  • Signalling mechanisms that contribute to the effects of parental exercise have been described for proteins, fatty acids, oligosaccharides and exerkines in the placenta and breast milk of exercised dams.

  • Paternal exercise effects might be explained by epigenetic adaptations observed in sperm of sires and tissues of their offspring, and short non-coding RNAs are emerging as potential epigenetic mediators of paternal exercise effects.

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Fig. 1: Maternal and paternal exercise improve the health of descendants through different actors and mechanisms that influence offspring tissues in a sex-specific manner.
Fig. 2: Proposed signalling mechanisms through which paternal exercise could improve the health of offspring.
Fig. 3: F0 generation exercise improves the health of F2 offspring born to F1 male or female offspring in a sex-specific manner.

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Acknowledgements

K.I.S. is supported by National Institutes of Health (NIH) Grants R01DK133859-01A1 to K.I.S. and the American Heart Association Grant AHA 23SFRNPCS1067042. E.F.-S. is supported by AHAPOST906327.

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Authors and Affiliations

  1. Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Elisa Félix-Soriano & Kristin I. Stanford

  2. Division of General and Gastrointestinal Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Elisa Félix-Soriano & Kristin I. Stanford

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  1. Elisa Félix-Soriano
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E.F.-S. researched data for the article. The authors contributed equally to all other aspects of the article.

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Correspondence to Kristin I. Stanford.

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Félix-Soriano, E., Stanford, K.I. Parental exercise mediates fetal metabolic and cardiac programming. Nat Rev Endocrinol (2025). https://doi.org/10.1038/s41574-025-01207-8

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