Paternal Exercise Confer's Endurance Capacity to Offspring Through Sperm MicroRNAs

A collaborative research team led by Chen-Yu Zhang, Xi Chen, and Di-Jun Chen from Nanjing University, together with Tao Zhang from Nanjing Medical University, has made groundbreaking findings in a study published in Cell Metabolism. The research demonstrates that sperm microRNAs act as carriers of epigenetic information, enabling the intergenerational transmission of paternal exercise capacity and metabolic health to offspring. This study provides the first evidence that exercise not only benefits individual physical fitness and metabolic profiles but also influences the physiological and metabolic characteristics of future generations.

Key Takeaways:

• Offspring sired by exercise-trained fathers exhibit intrinsic exercise adaptability and improved metabolic parameters compared to those from sedentary fathers.
• 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.
• Paternal PGC-1a, sperm microRNAs, and embryonic NCoR1 form a coherent molecular pathway through which exercise-induced endurance and metabolic adaptation are transmitted to the next generation via an intergenerational regulatory axis.
• Sperm microRNAs target NCoR1 in early embryos, resetting gene regulatory networks and reprogramming embryonic development.
• MicroRNAs are recognized as mobile signaling molecules that mediate communication between cells, tissues, and even across species, and this study reveals that sperm microRNAs facilitate crosstalk across generations.
• Paternal exercise can enhance glucose homeostasis in offspring by promoting glucose uptake in skeletal muscle.
• The study demonstrates that paternal exercise prior to conception can improve the health of future generations and help break the cycle of intergenerational obesity and chronic disease.

Statistics:

• The study finds that offspring of transgenic mice with muscle-specific overexpression of PGC-1a show improved endurance and metabolic traits, even in the absence of the inherited PGC-1a transgene.
• The injection of sperm small RNAs from exercised fathers into normal zygotes results in 75% of offspring exhibiting exercise-trained phenotypes.
• The study reveals that sperm microRNAs suppress nuclear receptor corepressor 1 (NCoR1) in early embryos, thereby reprogramming transcriptional networks to promote mitochondrial biogenesis and oxidative metabolism.

Sources:

• Yin et al. Paternal exercise confers endurance capacity to offspring through sperm microRNAs. Cell Metabolism. 6 October 2025.
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