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Sexually mature SD rats were randomly divided into a sham group (receiving 1% carboxymethyl cellulose sodium\u2009+\u2009standard chow, n\u2009=\u20099), a letrozole group (receiving LE\u2009+\u2009standard chow, n\u2009=\u200915), and a letrozole combined with HFD group (receiving LE\u2009+\u2009HFD, n\u2009=\u200915). After 21\u00a0days, model tests were performed based on body weight, estrous cycle, hormone levels, and ovarian histological changes, and successful modeling rats in LE and LE\u2009+\u2009HFD groups were further divided into two subgroups: an induction continuation group and an induction termination group (n\u2009=\u20096 in each group), respectively, which were treated for an additional 5\u00a0weeks. Changes in body weight, hormone levels, metabolic parameters, vaginal cytology, and ovarian histology were compared among the groups. Following 21\u00a0days of induction, the LE group exhibited significant differences in body weight, serum testosterone concentration, estrous cycle, and ovarian tissue morphology. The LE\u2009+\u2009HFD 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\u2009+\u2009HFD induction continuation group (LE\u2009+\u2009HFD-con group) were notably higher than those in the LE-con group, and ovarian histology were more severely disrupted. In conclusion,\u00a0the LE\u2009+\u2009HFD 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.<\/jats:p>","DOI":"10.1038\/s41598-025-15026-4","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T12:26:31Z","timestamp":1755779191000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Evaluation of representativeness and sustainability of PCOS rat models induced by letrozole with or without high-fat diet"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-8329","authenticated-orcid":false,"given":"Shanqin","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongshuai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-8189","authenticated-orcid":false,"given":"Kehua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"15026_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/nrendo.2018.24","volume":"14","author":"HF Escobar-Morreale","year":"2018","unstructured":"Escobar-Morreale, H. 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