Chronic cohabitation with CD1 male mice induces anxiety-like behaviors, reduced spontaneous alternation, dysregulated HPA axis, and disrupted sleep architecture in C57BL/6J female mice.

In contrast to the well-documented phenomena of inter-male aggression and competition in nature, the long-term consequences for females involuntarily exposed to persistent male-initiated social threat remain inadequately understood. In the present study, we demonstrate that C57BL/6J female mice co-housed with CD1 male mice for 14 days developed anxiety-like behaviors and cognitive deficits, without exhibiting depressive-like phenotypes. Concurrently, these females displayed a significant decrease in serum estrogen levels and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, co-housing with CD1 males profoundly disrupted sleep architecture in C57BL/6J females, as evidenced by reduced wakefulness and prolonged durations of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Mechanistically, these behavioral and physiological alterations were associated with substantial a reduction in cell density in the CA1 and CA3 subregions of the ventral hippocampus, accompanied by a marked downregulation of brain-derived neurotrophic factor (BDNF) within these same areas. Collectively, our findings provide experimental evidence for the adverse effects of chronic exposure to persistent male-initiated social threat on female recipients in a mammalian model, thereby offering a theoretical framework for understanding the enduring psychological trauma that may arise from sustained environments of psychological harassment, domestic violence, or sexual coercion-circumstances frequently encountered by women in human society.