Sex Differences in Reaction to Chronic Unpredictable Stress in the House Mouse (Mus musculus musculus) of Wild Origin

Sex differences in stress response continue to be understudied in basic physiological and behavioral research. The current study aimed to investigate the sex-specific effects of chronic stress in wild-derived house mice subjected to chronic unpredictable stress (CUS). The use of wild-derived mice enhanced the ecological validity of our stress model. We applied CUS for 5 weeks based on protocols previously established in laboratory mice, with regular weighting and welfare checks. Control mice were not subjected to stress. After the 5-week exposure, behavioral tests were performed, blood and hair samples were collected for corticosterone measurement, and stress-sensitive organ weights were assessed. Stressed females, but not stressed males, gained significantly less body weight over the entire CUS period. After CUS, mice tended to have higher adrenal and thymus weights. In stressed females, we observed significantly prolonged grooming time in the open field test and fewer immobility episodes in the tail suspension test (TST). Stressed males displayed significantly shorter immobility time in TST. Stressed males, but not stressed females, had significantly higher levels of hair corticosterone, with a similar tendency in plasma. Our results indicate different CUS coping strategies in males and females and raise a question about the development of different protocols for the assessment of stress responses in males and females.