Distinct HPO axis responses to chronic unpredictable stress in young versus adult female mice

Environmental and psychosocial stressors constitute major external determinants that accelerate the decline of ovarian function. As a classical paradigm for modeling chronic psychological stress, chronic unpredictable mild stress (CUMS) has been extensively employed to elucidate stress-induced perturbations in reproductive and endocrine homeostasis, as well as their contribution to the development of premature ovarian insufficiency (POI). Nevertheless, CUMS exposure initiated at different ages or administered for varying durations yields markedly heterogeneous physiological responses, and the extent to which these experimental conditions recapitulate the characteristics of long-term stress experienced by women in clinical settings remains insufficiently defined.Female C57BL/6 mice at 2 or 6 months of age were subjected to CUMS for 8 or 12 weeks. Endocrine profiling, hypothalamic–pituitary–ovarian (HPO) axis feedback responses, ovarian histology, and HPO axis transcriptomes were systematically analyzed.