by Nanjing University School of Life Sciences

Paternal exercise improves offspring endurance and metabolic health through sperm microRNAs that reprogram early embryonic gene expression, revealing how the benefits of exercise can be inherited across generations. Credit: Cell Metabolism

In a recent studypublishedinCell Metabolism, a research paper provides the first evidence that sperm microRNAs act as carriers of epigenetic information, enabling the intergenerational transmission of paternal exercise capacity and metabolic health, thereby exerting profound effects on offspring development.

The collaborative research team was led by Chen-Yu Zhang, Xi Chen, and Di-Jun Chen from Nanjing University, together with Tao Zhang from Nanjing Medical University, titled "Paternalexerciseconfers endurance capacity to offspring through sperm microRNAs."

Throughoutevolutionary history,exercise capacityhas been fundamental to human survival, with our ancestors relying on sustained physical performance for hunting, migration, and predator evasion. However, with the advent of modern society, human lifestyles have undergone dramatic changes. Sedentary behavior and physical inactivity have become the norm, making exercise seem less essential for survival.

Yet, a growing body of research reveals that the biological benefits of exercise continue to profoundly influence human health. Exercise not only enhances individual physical fitness and metabolic profiles—reducing the risk ofchronic diseases—but also exerts deeper effects on the physiological and metabolic characteristics of future generations. Nevertheless, the mechanisms through which paternal exercise influences offspring phenotypes remain poorly understood.

In this study, the authors demonstrate that offspring sired by exercise-trained fathers exhibit intrinsic exercise adaptability and improved metabolic parameters compared to those from sedentary fathers. Similarly, offspring of transgenic mice with muscle-specific overexpression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)—a key enhancer of mitochondrial function—also show improved endurance and metabolic traits, even in the absence of the inherited PGC-1α transgene.

Notably, the injection of sperm small RNAs from exercised fathers into normal zygotes reproduces exercise-trained phenotypes in the offspring at behavioral, metabolic, and molecular levels.

Mechanistically, both exercise training and muscular PGC-1α overexpression remodel the sperm microRNA profile, which directly suppresses nuclear receptor corepressor 1 (NCoR1), a functional antagonist of PGC-1α, in early embryos, thereby reprogramming transcriptional networks to promote mitochondrial biogenesis and oxidative metabolism. Overall, this study establishes a causal role for paternal PGC-1α, sperm microRNAs, and embryonic NCoR1 in mediating the transmission of exercise-induced phenotypes and metabolic adaptations to offspring.

The scientific significance of these findings is highlighted below:

More information: Paternal exercise confers endurance capacity to offspring through sperm microRNAs, Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.09.003 . www.cell.com/cell-metabolism/f … 1550-4131(25)00388-2 Journal information: Cell Metabolism

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Nanjing University School of Life Sciences