{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:07:23Z","timestamp":1790849243639,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","doi-asserted-by":"publisher","award":["IA206424"],"award-info":[{"award-number":["IA206424"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","doi-asserted-by":"publisher","award":["CF-2023-I-1588"],"award-info":[{"award-number":["CF-2023-I-1588"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","doi-asserted-by":"publisher","award":["1080127"],"award-info":[{"award-number":["1080127"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","doi-asserted-by":"publisher","award":["1191288"],"award-info":[{"award-number":["1191288"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","doi-asserted-by":"publisher","award":["FM\/DI\/058\/2023"],"award-info":[{"award-number":["FM\/DI\/058\/2023"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","doi-asserted-by":"publisher","award":["FM\/DI\/028\/2019"],"award-info":[{"award-number":["FM\/DI\/028\/2019"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","doi-asserted-by":"publisher","award":["IA206424"],"award-info":[{"award-number":["IA206424"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","doi-asserted-by":"publisher","award":["CF-2023-I-1588"],"award-info":[{"award-number":["CF-2023-I-1588"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","doi-asserted-by":"publisher","award":["1080127"],"award-info":[{"award-number":["1080127"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","doi-asserted-by":"publisher","award":["1191288"],"award-info":[{"award-number":["1191288"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","doi-asserted-by":"publisher","award":["FM\/DI\/058\/2023"],"award-info":[{"award-number":["FM\/DI\/058\/2023"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","doi-asserted-by":"publisher","award":["FM\/DI\/028\/2019"],"award-info":[{"award-number":["FM\/DI\/028\/2019"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, UNAM","award":["IA206424"],"award-info":[{"award-number":["IA206424"]}]},{"name":"Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, UNAM","award":["CF-2023-I-1588"],"award-info":[{"award-number":["CF-2023-I-1588"]}]},{"name":"Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, UNAM","award":["1080127"],"award-info":[{"award-number":["1080127"]}]},{"name":"Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, UNAM","award":["1191288"],"award-info":[{"award-number":["1191288"]}]},{"name":"Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, UNAM","award":["FM\/DI\/058\/2023"],"award-info":[{"award-number":["FM\/DI\/058\/2023"]}]},{"name":"Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, UNAM","award":["FM\/DI\/028\/2019"],"award-info":[{"award-number":["FM\/DI\/028\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligoanovulation, and polycystic ovarian morphology. Despite its classification as a reproductive disorder, PCOS is closely associated with metabolic dysregulation, including insulin resistance and obesity. An ideal animal model for PCOS should replicate both reproductive and metabolic features of the condition. In this study, we compared two widely used postnatal PCOS models (letrozole and estradiol valerate [EV]) administered alone or in combination with a high-fat diet (HFD), assessing their ability to induce both the reproductive and metabolic features. Letrozole treatment led to significant weight gain and increased visceral adiposity, effects that were amplified by HFD. Conversely, EV treatment showed a tendency toward reduced body mass. While neither model significantly altered fasting glucose levels, letrozole combined with HFD impaired glucose tolerance, supporting its role in metabolic dysfunction. Hyperandrogenism was more consistently induced by letrozole compared to EV, aligning with clinical PCOS phenotypes. Both treatments disrupted estrous cyclicity and induced polycystic ovarian morphology, though metabolic disturbances were more pronounced in the letrozole model. These findings suggest that letrozole, particularly in combination with HFD, provides a more consistent model for studying both the reproductive and metabolic facets of PCOS.<\/jats:p>","DOI":"10.3390\/biology14060592","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:35:09Z","timestamp":1747982109000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative Analysis of Letrozole and Estradiol Valerate PCOS Models: Reproductive and Metabolic Outcomes with and Without High-Fat Diet"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5251-0984","authenticated-orcid":false,"given":"X\u00f3chitl Acu\u00f1a","family":"Escalona","sequence":"first","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Posgrado en Cinecias Biol\u00f3gicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio Sarahy","family":"Ayala","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Posgrado en Cinecias Biol\u00f3gicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Cortez","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie Fern\u00e1ndez","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2495-1812","authenticated-orcid":false,"given":"Teresa","family":"Tom\u00e9-Dehesa","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-3497","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"D\u00edaz-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-195X","authenticated-orcid":false,"given":"Carlos","family":"Larqu\u00e9","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6559-6712","authenticated-orcid":false,"given":"Rene","family":"Escalona","sequence":"additional","affiliation":[{"name":"Laboratory of Embryology and Genetics, Departamento de Embriolog\u00eda y Gen\u00e9tica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16057","DOI":"10.1038\/nrdp.2016.57","article-title":"Polycystic ovary syndrome","volume":"2","author":"Azziz","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/AOG.0000000000002698","article-title":"Polycystic Ovary Syndrome","volume":"132","author":"Azziz","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1089\/jwh.2014.5000","article-title":"Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: Data from a large community-based cohort study","volume":"24","author":"Joham","year":"2015","journal-title":"J. Women\u2019s Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.1113\/JP277879","article-title":"Hyperandrogenism and insulin resistance-induced fetal loss: Evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome","volume":"597","author":"Zhang","year":"2019","journal-title":"J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.tem.2014.12.004","article-title":"Functional genomics of PCOS: From GWAS to molecular mechanisms","volume":"26","author":"McAllister","year":"2015","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e230342","DOI":"10.1530\/JOE-23-0342","article-title":"Hormonal changes in PCOS","volume":"261","author":"Yang","year":"2024","journal-title":"J. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1055\/s-2007-1009272","article-title":"Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease","volume":"21","author":"Mahabeer","year":"1989","journal-title":"Horm. Metab. Res."},{"key":"ref_8","first-page":"1241","article-title":"Defects in beta-cell function in functional ovarian hyperandrogenism","volume":"76","author":"Blackman","year":"1993","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"bnaa010","DOI":"10.1210\/endrev\/bnaa010","article-title":"Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome","volume":"41","author":"Padmanabhan","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/rmb2.12262","article-title":"Animal models of polycystic ovary syndrome: A review of hormone-induced rodent models focused on hypothalamus-pituitary-ovary axis and neuropeptides","volume":"18","author":"Osuka","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"174746","DOI":"10.1016\/j.ejphar.2022.174746","article-title":"Role of high-fat diet on letrozole-induced polycystic ovarian syndrome in rats","volume":"917","author":"Begum","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.reprotox.2017.10.005","article-title":"Neonatal exposure to estradiol valerate reprograms the rat ovary androgen receptor and anti-M\u00fcllerian hormone to a polycystic ovary phenotype","volume":"75","author":"Piquer","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1095\/biolreprod35.3.647","article-title":"Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat","volume":"35","author":"Brawer","year":"1986","journal-title":"Biol. Reprod."},{"key":"ref_14","first-page":"e922136","article-title":"A Rat Model of Polycystic Ovary Syndrome with Insulin Resistance Induced by Letrozole Combined with High Fat Diet","volume":"26","author":"Wang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.arcmed.2003.10.005","article-title":"Letrozole-induced polycystic ovaries in the rat: A new model for cystic ovarian disease","volume":"35","author":"Kafali","year":"2004","journal-title":"Arch. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.5653\/cerm.2013.40.3.115","article-title":"Stereological study of the effects of letrozole and estradiol valerate treatment on the ovary of rats","volume":"40","author":"Noorafshan","year":"2013","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.fertnstert.2012.07.1060","article-title":"Temporal window in which exposure to estradiol permanently modifies ovarian function causing polycystic ovary morphology in rats","volume":"98","author":"Cruz","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Larqu\u00e9, C., Lugo-Mart\u00ednez, H., Mendoza, X., Nochebuena, M., Novo, L., Vilchis, R., S\u00e1nchez-Bringas, G., Ubaldo, L., Velasco, M., and Escalona, R. (2023). Paternal Obesity Induced by High-Fat Diet Impairs the Metabolic and Reproductive Health of Progeny in Rats. Metabolites, 13.","DOI":"10.3390\/metabo13101098"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/10520290500138422","article-title":"A quantitative method for assessing stages of the rat estrous cycle","volume":"80","author":"Hubscher","year":"2005","journal-title":"Biotech. Histochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41574-024-01057-w","article-title":"Polycystic ovary syndrome as a metabolic disease","volume":"21","author":"Helvaci","year":"2025","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.111.097808","article-title":"Rodent models for human polycystic ovary syndrome","volume":"86","author":"Walters","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1210\/en.2007-0168","article-title":"A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome","volume":"148","author":"Cajander","year":"2007","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"bqac097","DOI":"10.1210\/endocr\/bqac097","article-title":"Distinctions in PCOS Induced by Letrozole vs Dehydroepiandrosterone with High-fat Diet in Mouse Model","volume":"163","author":"Poojary","year":"2022","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1095\/biolreprod.107.063974","article-title":"Neonatal exposure to estradiol valerate programs ovarian sympathetic innervation and follicular development in the adult rat","volume":"78","author":"Dorfman","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s12967-020-02519-1","article-title":"Impact of different omega-3 fatty acid sources on lipid, hormonal, blood glucose, weight gain and histopathological damages profile in PCOS rat model","volume":"18","author":"Komal","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13048-020-00633-8","article-title":"A combination of spearmint and flaxseed extract improved endocrine and histomorphology of ovary in experimental PCOS","volume":"13","author":"Mehraban","year":"2020","journal-title":"J. Ovarian Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R826","DOI":"10.1152\/ajpregu.00078.2005","article-title":"Effect of anti-NGF on ovarian expression of alpha1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries","volume":"290","author":"Manni","year":"2006","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1385\/ENDO:20:3:239","article-title":"Impact of estradiol on parametrial adipose tissue function: Evidence for establishment of a new set point of leptin sensitivity in control of energy metabolism in female rat","volume":"20","author":"Moreno","year":"2003","journal-title":"Endocrine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0091-3057(02)00732-3","article-title":"One injection of estradiol valerate induces dramatic changes in rats\u2019 intake of alcoholic beverages","volume":"72","author":"Reid","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1023\/A:1015953431333","article-title":"Effects of a brain-enhanced chemical delivery system for estradiol on body weight and food intake in intact and ovariectomized rats","volume":"6","author":"Simpkins","year":"1989","journal-title":"Pharm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Quirarte, G.L., Reid, L.D., de la Teja, I.S., Reid, M.L., S\u00e1nchez, M.A., D\u00edaz-Trujillo, A., Aguilar-Vazquez, A., and Prado-Alcal\u00e1, R.A. (2007). Estradiol valerate and alcohol intake: Dose-response assessments. BMC Pharmacol., 7.","DOI":"10.1186\/1471-2210-7-3"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1210\/jc.2016-2586","article-title":"Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women","volume":"101","author":"Dumesic","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jsbmb.2009.10.006","article-title":"A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats","volume":"122","author":"Alexanderson","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e923073","DOI":"10.12659\/MSM.923073","article-title":"Letrozole Rat Model Mimics Human Polycystic Ovarian Syndrome and Changes in Insulin Signal Pathways","volume":"26","author":"Xu","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1530\/REP-15-0352","article-title":"Letrozole vs estradiol valerate induced PCOS in rats: Glycemic, oxidative and inflammatory status assessment","volume":"151","author":"Lenghel","year":"2016","journal-title":"Reproduction"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102026","DOI":"10.1016\/j.npep.2020.102026","article-title":"Neuropeptide galanin and its effects on metabolic and reproductive disturbances in female rats with estradiol valerate (EV)-Induced polycystic ovary syndrome (PCOS)","volume":"80","author":"Azin","year":"2020","journal-title":"Neuropeptides"},{"key":"ref_37","first-page":"1215","article-title":"The Effect of Green Tea Extract on Reproductive Improvement in Estradiol Valerate-Induced Polycystic Ovarian Syndrome in Rat","volume":"14","author":"Ghafurniyan","year":"2015","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Barath, B., Varga, A., Matrai, A.A., Deak-Pocsai, K., Nemeth, N., and Deak, A. (2022). Estradiol Valerate Affects Hematological and Hemorheological Parameters in Rats. Metabolites, 12.","DOI":"10.3390\/metabo12070602"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rakic, D., Joksimovic Jovic, J., Jakovljevic, V., Zivkovic, V., Nikolic, M., Sretenovic, J., Nikolic, M., Jovic, N., Bicanin Ilic, M., and Arsenijevic, P. (2023). High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats. Medicina, 59.","DOI":"10.3390\/medicina59061104"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1530\/REP-17-0584","article-title":"High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats","volume":"155","author":"Patel","year":"2018","journal-title":"Reproduction"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E1076","DOI":"10.1152\/ajpendo.00182.2014","article-title":"Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model","volume":"308","author":"Ressler","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.steroids.2011.12.002","article-title":"Dyslipidemia in PCOS","volume":"77","author":"Wild","year":"2012","journal-title":"Steroids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1210\/en.2012-1693","article-title":"Continuous administration of a P450 aromatase inhibitor induces polycystic ovary syndrome with a metabolic and endocrine phenotype in female rats at adult age","volume":"154","author":"Maliqueo","year":"2013","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6674965","DOI":"10.1155\/2021\/6674965","article-title":"Effect of High-Fat Diet on the Intestinal Flora in Letrozole-Induced Polycystic Ovary Syndrome Rats","volume":"2021","author":"Zheng","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"108875","DOI":"10.1016\/j.steroids.2021.108875","article-title":"Does letrozole treatment have favorable effects on the lipid profile? A systematic review and meta-analysis of randomized clinical trials","volume":"172","author":"Cai","year":"2021","journal-title":"Steroids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.9734\/ARRB\/2015\/14749","article-title":"Effect of Estradiol Valerate on Serum Biochemical Profiles in Aged Female Albino Rats","volume":"6","author":"Lalithamma","year":"2014","journal-title":"Annu. Res. Rev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s40618-020-01351-0","article-title":"Insulin resistance and PCOS: Chicken or egg?","volume":"44","author":"Moghetti","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1023\/A:1005937900788","article-title":"Effect of CGS 20267 on ovarian aromatase and gonadotropin levels in the rat","volume":"48","author":"Sinha","year":"1998","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.bbrc.2017.01.057","article-title":"The effects of 6-Gingerol on reproductive improvement, liver functioning and Cyclooxygenase-2 gene expression in estradiol valerate\u2014Induced polycystic ovary syndrome in Wistar rats","volume":"484","author":"Pournaderi","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/6\/592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:39:00Z","timestamp":1760031540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/6\/592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biology14060592"],"URL":"https:\/\/doi.org\/10.3390\/biology14060592","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]}}}