Abstract
CONTEXT: Irisin, a cleaved product of fibronectin type III domain-containing protein 5 (FNDC5), has been proposed as a key molecular link between energy metabolism and reproductive regulation. Emerging evidence suggests that it modulates hypothalamic-pituitary-gonadal (HPG) activity and oxidative balance, but its reproductive effects in males remain insufficiently defined. OBJECTIVE: To evaluate the endocrine, antioxidant, and reproductive responses to exogenous irisin administration in healthy male Wistar rats. DESIGN: A controlled, time-course experimental study was conducted to assess hormonal, biochemical, and sperm-related outcomes following irisin treatment. SUBJECTS AND METHODS: Twenty-four adult male Wistar rats were randomly allocated to Control (saline) or Treated (irisin, 200 ng/kg, subcutaneous) groups, with sample collection on days 10, 20, and 30. Serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, lipid profiles, and oxidative stress biomarkers [malondialdehyde (MDA), reactive oxygen species (ROS), total antioxidant capacity (TAC)] were analyzed. Sperm count, motility, and morphology were also evaluated. RESULTS: Irisin administration significantly increased serum GnRH, LH, FSH, and testosterone concentrations (p < 0.001), indicating activation of the HPG axis. Lipid parameters remained unchanged. Oxidative stress markers were favorably modulated, with reduced MDA and ROS (p < 0.05) and a progressive increase in TAC over time (p < 0.05, group × day interaction). Sperm count was higher in the Treated group (p < 0.05), while motility and morphology were not significantly affected. CONCLUSIONS: Subcutaneous irisin administration enhances reproductive hormone secretion, improves antioxidant capacity, and increases sperm production in male rats without altering lipid metabolism. These findings suggest that irisin may serve as a potential therapeutic modulator of male reproductive function, particularly under conditions involving oxidative stress or endocrine disruption.