{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:36:12Z","timestamp":1786448172664,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Junior Project Faculty of Medical Sciences, University of Kragujevac, Serbia","award":["11\/24"],"award-info":[{"award-number":["11\/24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background\/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine\u2013metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1\u03b2, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/pathophysiology33030061","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:32:16Z","timestamp":1786444336000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reproductive and Cardiometabolic Characterization of a Letrozole- and High-Fat Diet-Induced PMOS-like Rat Model: An Experimental Study"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3912-5404","authenticated-orcid":false,"given":"Milica","family":"Milinkovic Sorgic","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3023-0478","authenticated-orcid":false,"given":"Aleksandar","family":"Matic","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0071-8376","authenticated-orcid":false,"given":"Vladimir","family":"Jakovljevic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Department of Human Pathology, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-1577","authenticated-orcid":false,"given":"Nikola","family":"Jovic","sequence":"additional","affiliation":[{"name":"University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sladjana","family":"Novakovic","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Todorovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7799-6264","authenticated-orcid":false,"given":"Jovan","family":"Milosavljevic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7603-5865","authenticated-orcid":false,"given":"Bozidar","family":"Pindovic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5849-1998","authenticated-orcid":false,"given":"Jasmina","family":"Sretenovic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Canovic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Jakovljevic Uzelac","sequence":"additional","affiliation":[{"name":"Institute of Medical Physiology \u201cRichard Burian\u201d, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-0626","authenticated-orcid":false,"given":"Jovana","family":"Joksimovic Jovic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/S0140-6736(26)00717-8","article-title":"Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: A multistep global consensus process","volume":"407","author":"Teede","year":"2026","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Islam, H., Masud, J., Islam, Y.N., and Haque, F.K.M. 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