Endurance Training Attenuates Acute Exercise-Induced Monocyte Transcriptomic Responses in Adolescents: Sex-Specific Molecular Adaptations

Background: Circulating monocytes contribute to atherogenesis and vascular dysfunction. Although clinical cardiovascular disease presents in adulthood, its biological origins often begin in youth and differ substantially between females and males. Methods: Twelve males and nine females (14-17 years) completed an acute exercise protocol consisting of ten 2-min cycling bouts at 70% of maximal work rate interspersed with 1-min rest intervals, performed before and after an 8-week supervised endurance training intervention with brief supplementary strength work (60 min/session, 3 sessions/week). Blood was collected before and immediately after each exercise challenge. Peripheral blood monocytes were isolated and whole-transcriptome RNA sequencing (RNA-seq) was performed. Results: Prior to training, acute exercise induced a markedly greater monocyte transcriptomic response in females compared with males (5,135 vs. 567 differentially expressed transcripts, FDR < 0.1). Pathway analyses identified vascular function–related pathways in males, whereas females showed enrichment of pathways related to adipose tissue crosstalk and oxidative metabolism. Following training, the acute transcriptomic response was markedly attenuated in both sexes (165 transcripts in males and 94 in females, FDR < 0.1), representing an approximately 98% reduction in females and a ~70% reduction in males relative to pre-training responses. Conclusion: These findings reveal sex-specific monocyte responses to acute exercise in youth and suggest that endurance exercise alters immune transcriptional responsiveness in pathways relevant to vascular and cardiovascular health.