Effects of chronic unpredictable mild stress on ovarian reserve in female rats: Feasibility analysis of a rat model of premature ovarian failure

Premature ovarian failure (POF) results from a number of disorders. The POF model is primarily based on chemotherapeutic injury, and hence is not suitable for assessing the effects of chronic stress on ovarian function. Therefore, improved animal models are required to analyze the effects of chronic stress on ovarian reserve. The feasibility of the chronic unpredictable mild stress (CUMS) method for establishing a model of POF was examined. The depressive behavior exhibited by rats was evaluated with the open field and sucrose preference tests. Vaginal smears were obtained for assessment of the estrous cycle. The ovarian reserve of the animals was evaluated using the estrous cycle, ovarian histology and serum levels of gonadotropin releasing hormone (GnRH), follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mfillerian hormone (AMH). Compared with the control group, body weight, time spent in the center, horizontal movement, vertical frequency, consumption of sucrose, sucrose preference, number of small follicles from the rats, and serum E2, AMH and GnRH levels were significantly decreased in the CUMS group (all P<0.05). However, the estrous cycle was prolonged significantly (P<0.05) and serum FSH levels were increased significantly (P<0.01). These results suggested that the CUMS model rats exhibited depression-like behaviors. CUMS may induce psychological stress and decrease ovarian reserve in female rats. Thus, the CUMS model may be used to assess the effects of chronic stress on female reproductive function.