Biological Sex Differences In Blood-Based Biomarkers After Physiological Exercise Testing In Endurance-Trained Athletes

PURPOSE: Load monitoring tools are used to determine the physiological response to exercise. In particular, objective parameters such as blood-based biomarkers can provide valuable insights into various physiological domains such as training load, training stress, immune, and inflammatory response. However, these responses can be influenced by training status, age, and sex. The aim of the present study was to assess the acute exercise responses of several established and novel biomarkers with respect to biological sex. METHODS: Twenty-four healthy, endurance-trained participants (male: n = 16, age: 29.2 ± 7.6 yrs, weight: 74.9 ± 7.8 kg, height: 181.0 ± 6.5 cm, maximal oxygen uptake (VO2max): 59.4 ± 7.5 ml·min-1·kg-1 ; female: n = 8, age: 26.8 ± 6.1 yrs, weight: 59.5 ± 9.0 kg, height: 168.6 ± 5.5 cm, VO2max: 52.5 ± 3.1 ml·min-1·kg-1) were subjected to an incremental submaximal exercise test, followed by an 8 min recovery period, and a ramp test until voluntary exhaustion. Venous blood samples were obtained prior to the incremental test and immediately after the ramp test. We analyzed whole blood count via hematology analyzer, cell-free DNA (cfDNA with 90 and 222 base pairs) via quantitative real-time PCR as well as creatine kinase (CK) via light emitting diode photometer. Acute changes in blood parameters were analyzed using pairwise t-test or Wilcoxon-test, and sex by time interactions via mixed ANOVA. RESULTS: Significant changes (p < 0.001) from pre to post-exercise were observed for cfDNA90 (11.3-fold), cfDNA222 (10.8-fold), percentage (1.3-fold) and absolute lymphocytes (LYM; 2.7-fold), absolute monocytes (2.3-fold), white blood count (WBC; 2.0-fold), percentage (0.9-fold) and absolute granulocytes (GR; 1.8-fold), CK, platelets, procalcitonin (PCT; all 1.4-fold), hemoglobin, hematocrit, and red blood count (all 1.1- fold). Significant sex by time interactions (p < 0.05) were found for cfDNA90 (male: 12.5- vs. female: 7.2-fold), cfDNA222 (11.6 vs. 8.7-fold), LYM (2.6- vs. 3.1-fold), WBC (1.9- vs. 2.4-fold), GR (1.7- vs. 2.0-fold), and PCT (1.4- vs. 1.3-fold). CONCLUSIONS: Our study identified load sensitive biomarkers in an acute exercise setting. Furthermore, the analysis suggested sex specific responses in some variables of the whole blood count and cfDNA in endurance-trained athletes.