Evaluation of representativeness and sustainability of PCOS rat models induced by letrozole with or without high-fat diet.

This article aimed to evaluate the representativeness and sustainability of a rat model of polycystic ovary syndrome (PCOS) induced by letrozole (LE) with or without a high-fat diet (HFD). Sexually mature SD rats were randomly divided into a sham group (receiving 1% carboxymethyl cellulose sodium + standard chow, n = 9), a letrozole group (receiving LE + standard chow, n = 15), and a letrozole combined with HFD group (receiving LE + HFD, n = 15). After 21 days, model tests were performed based on body weight, estrous cycle, hormone levels, and ovarian histological changes, and successful modeling rats in LE and LE + HFD groups were further divided into two subgroups: an induction continuation group and an induction termination group (n = 6 in each group), respectively, which were treated for an additional 5 weeks. Changes in body weight, hormone levels, metabolic parameters, vaginal cytology, and ovarian histology were compared among the groups. Following 21 days of induction, the LE group exhibited significant differences in body weight, serum testosterone concentration, estrous cycle, and ovarian tissue morphology. The LE + HFD group showed significant increases in serum lipid and insulin levels. Upon subdivision, the PCOS phenotype in the letrozole continuation induction group (LE-con group) persisted, while it gradually subsided in the termination group (LE-ter group). Body weight, fasting insulin levels, and the homeostasis model assessment of insulin resistance index in the LE + HFD induction continuation group (LE + HFD-con group) were notably higher than those in the LE-con group, and ovarian histology were more severely disrupted. In conclusion, the LE + HFD induced rats more closely mimic the pathological characteristics of clinical PCOS and thus represent a more representative model compared to those induced by LE alone. However, both models tend to recover after discontinuation, indicating that medication should be continued during subsequent treatment to ensure the sustainability of the models.