Dose- and time-dependent effects of intravenous irisin administration on GnRH, LH, FSH, and estrogen in Kurdish ewes during the breeding season

Efficient reproduction in seasonally breeding ewes hinges on a precise integration of metabolic cues and the hypothalamic–pituitary–gonadal (HPG) axis. This study investigated the dose- and time-dependent effects of intravenous administration of irisin on reproductive (GnRH, LH, FSH, and estrogen) and metabolic (glucose, insulin, leptin) hormones in Kurdish ewes during the breeding season. Twenty-four clinically healthy ewes were randomly assigned to four groups (n = 6 each): Control (saline), Low-dose (10 ng/kg), Medium-dose (20 ng/kg), and High-dose (40 ng/kg) irisin. Treatments were administered every three days for 45 days, and blood samples were collected up to Day 60. Estrous cycle phase (luteal or follicular), confirmed by progesterone measurements and behavioral observations, did not differ among groups. Medium- and high-dose irisin elicited significant increases in GnRH, LH, FSH, and estrogen concentrations, particularly on Days 30 and 45, whereas low-dose irisin produced minimal endocrine effects. Insulin and leptin also increased markedly in the medium- and high-dose groups, suggesting a parallel dose-related impact on metabolic pathways. By Day 60, reproductive hormone levels returned near baseline, indicating that continuous irisin exposure is required to sustain these changes. Correlation analyses revealed that insulin and leptin are intricately linked to gonadotropin and estrogen variations, underscoring irisin's role as a metabolic-reproductive mediator. These findings imply that exogenous irisin can modulate reproductive function in ewes by coordinating metabolic and endocrine signals, offering potential applications for managing fertility in seasonally breeding ruminants.