Mood, hormone levels, metabolic and sleep across the menopausal transition in VCD-induced ICR mice

Menopausal transition is the transitional period before menopause in women, often accompanied by abnormal fluctuations in hormone levels that increase the risk of aging-related diseases. 4-vinylcyclohexene dioxide (VCD) is a chemical agent that induces gradual depletion of ovarian follicles, which can mimic the natural human process of transition from menopausal transition to post-menopause. Previous studies have shown that the onset of menopausal transition or menopause in VCD-injected mice is associated with a specific strain, even in inbred animals. Institute of Cancer Research (ICR) mice constitute general purpose outbred population, which has not been well-characterized in the VCD-induced model. Thus, the current study aimed to explore the characteristic features, including sleep, mood, and metabolism, of the model by examining the effect of timing of VCD injection in ICR mice to extend the applications of this model.

ICR mice were randomly divided into six groups: 20d VCD and 20d Control, 35d VCD and 35d Control, 52d VCD and 52d Control. VCD mice were intraperitoneally injected with VCD (160 mg/kg), while Control mice were injected intraperitoneally with sesame oil for 4 consecutive weeks, five times a week daily. A vaginal smear was used to observe the estrous cycle of the mice. On the 20th, 35th, and 52nd day after VCD or sesame oil injection, the ovarian morphology, the number of atretic cells, hormone levels, anxiety, depression-like behaviors, sleep phase, and energy metabolism were observed.

The menopausal transition model was successfully replicated by injecting VCD into ICR mice. On the specific days after VCD treatment, the number of atretic follicles increased, the level of E2 decreased and FSH increased, the depressive- and anxiety-like behavior increased, the time of REM and NREM sleep time decreased, and energy metabolism was reduced.

These results suggested that the ICR mice model has human-like characteristics during the menopause transition. Moreover, the ICR model has a long menopausal transition duration.