Influence of biological sex on exercise-induced nuclear factor erythroid 2-related factor 2 and downstream targets

Objective: To evaluate whether exercise induces different nuclear factor erythroid 2-related factor 2 (NRF2) responses in males and females. Methods: 22 males and females (n=11 per group; mean [SD]: age: 25 [6] years, height: 1.71 [0.10] m, weight: 69.6 [12.3] kg) performed 100 drop jumps and 50 squat jumps. NRF2/antioxidant response element (ARE) binding in peripheral blood mononuclear cells, glutathione peroxidase (GPX) activity, and immune markers influenced by NRF2 (interleukin- 6 [IL-6], tumour necrosis factor-α [TNF-α], matrix metalloproteinase-9 [MMP-9], vascular cell adhesion molecule-1 [VCAM-1], total leukocytes, neutrophils, monocytes) were measured pre-, post-, and 1 h post-exercise. Results: NRF2/ARE binding did not significantly alter following exercise (p=0.59) and no sex differences were evident (p=0.17). Similarly, GPX activity did not change post-exercise (p=0.74) and did not differ between sexes (p=0.61). IL-6 and TNF-α did not increase post- exercise (p>0.05 for both) but were lower in females (p<0.01 for both). MMP-9 increased post-exercise (p=0.02), but no group differences were found (p=0.27). VCAM-1 was unchanged after exercise (p=0.38) and did not differ between groups (p=0.11). Total leukocytes, neutrophil, and monocytes all increased post-exercise (p<0.01 for all); neutrophils were lower (p<0.01), and monocytes higher (p=0.03) in females vs. males. Conclusion: There were no sex differences in NRF2 activity at rest and in response to an exercise bout, however, several immune markers displayed sex-specific differences, independent to NRF2. Significance: Sex differences in NRF2 signalling were not evident, suggesting males and females may incur similar redox-specific adaptations post-exercise.