Regulatory Mechanisms and Safety Evaluation of Exogenous Progesterone for Suppression of Rutting Behavior in Male Sika Deer (Cervus nippon)

Managing rutting aggression is critical in sika deer (Cervus nippon) farming. To mitigate rutting aggression in male sika deer, this study evaluated the efficacy, safety, and physiological mechanisms of exogenous progesterone. Twelve sika deer were randomly assigned to either a control group or a treatment group, with behavior monitored for 60 days post-administration. Serum hormones, non-targeted serum metabolomics, biochemical indicators (including reflecting liver and kidney function), and subsequent antler performance were assessed. The treatment group exhibited significantly reduced aggressive and mating behavior throughout the study (p < 0.05). HPG axis hormones (GnRH, LH, FSH, and T) and PRL were significantly reduced throughout the study (p < 0.05), while TRH was elevated, T4 declined, and GH showed time-dependent fluctuations. Differential metabolites were significantly enriched in pathways related to nucleotide metabolism, pyruvate metabolism, and arachidonic acid metabolism. Except for a transient decrease in the ALB/GLB ratio (p < 0.05), no significant changes were observed in other biochemical indicators or antler performance (p > 0.05). This study confirms that exogenous progesterone effectively controls rutting behavior primarily via HPG-axis suppression and multi-system endocrine interactions, without inducing detectable organ toxicity or compromising production, supporting its use as a safe management intervention.