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 (<i>Cervus nippon</i>) 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 (<i>p</i> < 0.05). HPG axis hormones (GnRH, LH, FSH, and T) and PRL were significantly reduced throughout the study (<i>p</i> < 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 (<i>p</i> < 0.05), no significant changes were observed in other biochemical indicators or antler performance (<i>p</i> > 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.