Extracellular vesicle characteristics differ between sexes following exercise training

The benefits of combining resistance and endurance training have been extensively studied and celebrated. However, recent research suggests that the way our bodies respond to exercise may differ between men and women, influenced by hormonal and genetic factors. Extracellular vesicles (EVs) are tiny particles released by cells that play a crucial role in cellular communication and signaling.

Researchers at the University of Pittsburgh set out to investigate whether the characteristics of EVs differ between men and women following concurrent resistance and endurance exercise training (CET). Eighteen young, healthy participants embarked on a 12-week CET program, which involved a combination of resistance and endurance exercises. Before and after the training program, participants performed an acute bout of heavy resistance exercise (AHRET) to assess the immediate effects on EVs.

Schematic overview of study methodology

Prior to the chronic training program subjects had blood draws taken before and after an acute bout of heavy resistance exercise training (AHRET, acute bout of heavy resistance exercise; 6 × 10 at 75% 1 RM on the back squat). Subjects then underwent 12 weeks of resistance exercise training, following which they repeated the AHRET bout. Extracellular vesicles (EVs) were isolated from plasma samples via a combined size exclusion chromatography and ultrafiltration technique (SEC-UF). EV characteristics and contents were analyzed via Nanoparticle Tracking Analysis, Imaging Flow Cytometry, and small RNA sequencing.

The findings revealed intriguing insights into how EVs respond to exercise, particularly in relation to sex differences. Following AHRET, the abundance of EVs increased significantly in trained men but not in women, indicating a distinct response to exercise between the sexes. Moreover, changes in muscle-derived EVs and microvesicles were observed, suggesting a specific impact on muscle-related signaling pathways.

Perhaps most strikingly, the study uncovered notable differences in the miRNA contents of EVs between men and women. MiRNAs, small RNA molecules involved in gene regulation, showed larger variations in men following the 12-week training program compared to women, both at rest and after exercise. Pathway analysis based on these differentially expressed EV miRNAs revealed that exercise training may have a more pronounced effect on hypertrophy and growth pathways in men compared to women.

These findings shed light on the intricate interplay between exercise, EVs, and sex-based differences in adaptive signaling. The study suggests that EVs may serve as important mediators of the body’s response to exercise, with potential implications for optimizing training strategies and personalized exercise prescriptions.

This research underscores the importance of considering sex-specific differences in exercise physiology and highlights the potential role of EVs as key players in the adaptive response to exercise. By unraveling the complexities of EV signaling in the context of exercise, we move closer to a deeper understanding of how our bodies adapt and thrive in response to physical activity.

Kargl CK, Sterczala AJ, Santucci D, Conkright WR, Krajewski KT, Martin BJ, Greeves JP, O’Leary TJ, Wardle SL, Sahu A, Ambrosio F, Nindl BC. (2024) Circulating extracellular vesicle characteristics differ between men and women following 12 weeks of concurrent exercise training. Physiol Rep 12(9):e16016. [article]

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