{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:02:55Z","timestamp":1790856175184,"version":"4.1.0"},"reference-count":173,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T00:00:00Z","timestamp":1559520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["2016R1E1A1A01943455"],"award-info":[{"award-number":["2016R1E1A1A01943455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hormonal disturbances, such as hyperandrogenism, are considered important for developing polycystic ovary syndrome (PCOS) in humans. Accordingly, directly hormone-regulated animal models are widely used for studying PCOS, as they replicate several key PCOS features. However, the pathogenesis and treatment of PCOS are still unclear. In this review, we aimed to investigate animal PCOS models and PCOS-like phenotypes in animal experiments without direct hormonal interventions and determine the underlying mechanisms for a better understanding of PCOS. We summarized animal PCOS models that used indirect hormonal interventions and suggested or discussed pathogenesis of PCOS-like features in animals and PCOS-like phenotypes generated in other animals. We presented integrated physiological insights and shared cellular pathways underlying the pathogenesis of PCOS in reviewed animal models. Our review indicates that the hormonal and metabolic changes could be due to molecular dysregulations, such as upregulated PI3K-Akt and extracellular signal-regulated kinase (ERK) signalling, that potentially cause PCOS-like phenotypes in the animal models. This review will be helpful for considering alternative animal PCOS models to determine the cellular\/molecular mechanisms underlying PCOS symptoms. The efforts to determine the specific cellular mechanisms of PCOS will contribute to novel treatments and control methods for this complex syndrome.<\/jats:p>","DOI":"10.3390\/ijms20112720","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T11:31:01Z","timestamp":1559561461000},"page":"2720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Animal Models for Human Polycystic Ovary Syndrome (PCOS) Focused on the Use of Indirect Hormonal Perturbations: A Review of the Literature"],"prefix":"10.3390","volume":"20","author":[{"given":"Youngjae","family":"Ryu","sequence":"first","affiliation":[{"name":"Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-519X","authenticated-orcid":false,"given":"Yoon Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-854X","authenticated-orcid":false,"given":"Seung-Yup","family":"Ku","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod., 19, 41\u201347.","DOI":"10.1093\/humrep\/deh098"},{"key":"ref_2","first-page":"134","article-title":"On the association of continued cornification of the vaginal mucosa with the presence of large vesicles in the ovary and the absence of corpus formation","volume":"60","author":"Evans","year":"1921","journal-title":"Anat. Rec. XXI"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/humrep\/dex036","article-title":"Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys","volume":"32","author":"Abbott","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/humupd\/dmt061","article-title":"Definition and significance of polycystic ovarian morphology: A task force report from the androgen excess and polycystic ovary syndrome society","volume":"20","author":"Dewailly","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mce.2013.01.013","article-title":"Nonhuman primate models of polycystic ovary syndrome","volume":"373","author":"Abbott","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11154-007-9046-0","article-title":"Polycystic ovary syndrome and its developmental origins","volume":"8","author":"Dumesic","year":"2007","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1210\/en.2012-1366","article-title":"Animal models and the developmental origins of polycystic ovary syndrome: Increasing evidence for the role of androgens in programming reproductive and metabolic dysfunction","volume":"153","author":"Franks","year":"2012","journal-title":"Endocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.lfs.2017.10.020","article-title":"Hormone-induced rat model of polycystic ovary syndrome: A systematic review","volume":"191","author":"Noroozzadeh","year":"2017","journal-title":"Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.steroids.2013.05.004","article-title":"Animal models of the polycystic ovary syndrome phenotype","volume":"78","author":"Padmanabhan","year":"2013","journal-title":"Steroids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12958-017-0231-z","article-title":"Animal models of hyperandrogenism and ovarian morphology changes as features of polycystic ovary syndrome: A systematic review","volume":"15","author":"Paixao","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.fertnstert.2012.04.006","article-title":"Animal models of polycystic ovary syndrome: A focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk","volume":"98","author":"Shi","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.repbio.2013.09.007","article-title":"Mouse models to study polycystic ovary syndrome: A possible link between metabolism and ovarian function?","volume":"14","author":"Visser","year":"2014","journal-title":"Reprod. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","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_14","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.beem.2018.03.008","article-title":"Evidence from animal models on the pathogenesis of PCOS","volume":"32","author":"Walters","year":"2018","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1507\/endocrj.K09E-205","article-title":"Endocrine traits of polycystic ovary syndrome in prenatally androgenized female sprague-dawley rats","volume":"57","author":"Wu","year":"2010","journal-title":"Endocr. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.yhbeh.2007.12.013","article-title":"Neuroendocrine consequences of androgen excess in female rodents","volume":"53","author":"Foecking","year":"2008","journal-title":"Horm. Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"99405","DOI":"10.1172\/jci.insight.99405","article-title":"Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS","volume":"3","author":"Silva","year":"2018","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41591-018-0035-5","article-title":"Elevated prenatal anti-mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood","volume":"24","author":"Tata","year":"2018","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1210\/jc.2006-0178","article-title":"Positions statement: Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An androgen excess society guideline","volume":"91","author":"Azziz","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/humrep\/dep049","article-title":"Androgen circle of polycystic ovary syndrome","volume":"24","author":"Homburg","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/humupd\/dml017","article-title":"The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome","volume":"12","author":"Blank","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.molmed.2006.05.006","article-title":"Molecular mechanisms of insulin resistance in polycystic ovary syndrome","volume":"12","author":"Papavassiliou","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1093\/humrep\/deu198","article-title":"The striking similarities in the metabolic associations of female androgen excess and male androgen deficiency","volume":"29","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/humupd\/dmw027","article-title":"Interactions between androgens, fsh, anti-mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary","volume":"22","author":"Dewailly","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1056\/NEJMra041536","article-title":"Polycystic ovary syndrome","volume":"352","author":"Ehrmann","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1210\/en.2008-1575","article-title":"Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans","volume":"150","author":"Dissen","year":"2009","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1210\/en.2014-1368","article-title":"Excess of nerve growth factor in the ovary causes a polycystic ovary-like syndrome in mice, which closely resembles both reproductive and metabolic aspects of the human syndrome","volume":"155","author":"Wilson","year":"2014","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mce.2010.05.003","article-title":"The lack of estrogen and excess luteinizing hormone are responsible for the female ArKO mouse phenotype","volume":"327","author":"Liew","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1073\/pnas.92.5.1322","article-title":"Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors","volume":"92","author":"Risma","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1210\/endo.138.8.5313","article-title":"Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology","volume":"138","author":"Risma","year":"1997","journal-title":"Endocrinology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1210\/en.2008-1774","article-title":"Theca-specific estrogen receptor-alpha knockout mice lose fertility prematurely","volume":"150","author":"Lee","year":"2009","journal-title":"Endocrinology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00795-009-0466-7","article-title":"Increased ovarian follicle atresia in obese zucker rats is associated with enhanced expression of the forkhead transcription factor foxo1","volume":"42","author":"Kajihara","year":"2009","journal-title":"Med. Mol. Morphol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1477-7827-8-73","article-title":"Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant zucker fatty (fa\/fa) rats","volume":"8","author":"Honnma","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1530\/JOE-11-0022","article-title":"The new zealand obese mouse model of obesity insulin resistance and poor breeding performance: Evaluation of ovarian structure and function","volume":"209","author":"Blair","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1210\/endo.138.10.5428","article-title":"Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the new zealand obese mouse","volume":"138","author":"Igel","year":"1997","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1006\/bbrc.1996.1133","article-title":"Molecular cloning of rat leptin receptor isoform complementary dnas--identification of a missense mutation in zucker fatty (fa\/fa) rats","volume":"225","author":"Takaya","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrendo.2018.24","article-title":"Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment","volume":"14","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E7187","DOI":"10.1073\/pnas.1708854114","article-title":"Adiponectin protects against development of metabolic disturbances in a PCOS mouse model","volume":"114","author":"Benrick","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamcr.2011.03.010","article-title":"Akt, foxo and regulation of apoptosis","volume":"1813","author":"Zhang","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1210\/en.2008-1612","article-title":"A unique rodent model of cardiometabolic risk associated with the metabolic syndrome and polycystic ovary syndrome","volume":"150","author":"Shi","year":"2009","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/humrep\/12.suppl_1.53","article-title":"Insulin regulation of human ovarian androgens","volume":"12","author":"Nestler","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1006\/bbrc.1996.0951","article-title":"Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not zucker (fa\/fa) rats as measured by elisa","volume":"223","author":"Hardie","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1210\/en.2014-1185","article-title":"Angiotensin ii type 2 receptor stimulation improves fatty acid ovarian uptake and hyperandrogenemia in an obese rat model of polycystic ovary syndrome","volume":"155","author":"Leblanc","year":"2014","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cmet.2010.03.002","article-title":"Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility","volume":"11","author":"Hill","year":"2010","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Marino, J.S., Iler, J., Dowling, A.R., Chua, S., Bruning, J.C., Coppari, R., and Hill, J.W. (2012). Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS): Evidence of adipocyte hypertrophy and tissue-specific inflammation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048643"},{"key":"ref_47","first-page":"825","article-title":"Prohibitin-induced obesity leads to anovulation and polycystic ovary in mice","volume":"6","author":"Ande","year":"2017","journal-title":"Biol. Open"},{"key":"ref_48","first-page":"403","article-title":"Loss of pkbbeta\/akt2 predisposes mice to ovarian cyst formation and increases the severity of polycystic ovary formation in vivo","volume":"5","author":"Restuccia","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1126\/science.292.5522.1728","article-title":"Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta)","volume":"292","author":"Cho","year":"2001","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.mce.2017.01.043","article-title":"Selective deletion of pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice","volume":"444","author":"Lan","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.1210\/endo.140.12.7222","article-title":"Prevention of the polycystic ovarian phenotype and characterization of ovulatory capacity in the estrogen receptor-alpha knockout mouse","volume":"140","author":"Couse","year":"1999","journal-title":"Endocrinology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1210\/me.2002-0398","article-title":"Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (er) null mice reveals hypergonadism and endocrine sex reversal in females lacking eralpha but not erbeta","volume":"17","author":"Couse","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1210\/en.2004-0548","article-title":"Formation of cystic ovarian follicles associated with elevated luteinizing hormone requires estrogen receptor-beta","volume":"145","author":"Couse","year":"2004","journal-title":"Endocrinology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.1073\/pnas.95.12.6965","article-title":"Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene","volume":"95","author":"Fisher","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1210\/endo.141.7.7578","article-title":"An age-related ovarian phenotype in mice with targeted disruption of the cyp 19 (aromatase) gene","volume":"141","author":"Britt","year":"2000","journal-title":"Endocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12735","DOI":"10.1073\/pnas.97.23.12735","article-title":"Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity","volume":"97","author":"Jones","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"E812","DOI":"10.1152\/ajpendo.00367.2002","article-title":"Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion","volume":"285","author":"Kero","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1210\/endo.142.11.8472","article-title":"Gonadal pathologies in transgenic mice expressing the rat inhibin alpha-subunit","volume":"142","author":"McMullen","year":"2001","journal-title":"Endocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/0303-7207(91)90234-J","article-title":"Effect of recombinant inhibin on androgen synthesis in cultured human thecal cells","volume":"75","author":"Hillier","year":"1991","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1677\/JME-06-0057","article-title":"Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice","volume":"39","author":"Devin","year":"2007","journal-title":"J. Mol. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1111\/j.1538-7836.2005.01390.x","article-title":"On the role of plasminogen activator inhibitor-1 in adipose tissue development and insulin resistance in mice","volume":"3","author":"Lijnen","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1161\/01.ATV.0000242905.41404.68","article-title":"Pai-1 and the metabolic syndrome: Links, causes, and consequences","volume":"26","author":"Alessi","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"341583","DOI":"10.1155\/2015\/341583","article-title":"Relevance of sympathetic nervous system activation in obesity and metabolic syndrome","volume":"2015","author":"Thorp","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bbrc.2012.09.099","article-title":"Polycystic ovary syndrome (PCOS)-like phenotypes in the d-galactose-induced aging mouse model","volume":"427","author":"Park","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"943694","DOI":"10.1155\/2015\/943694","article-title":"Manifestation of hyperandrogenism in the continuous light exposure-induced PCOS rat model","volume":"2015","author":"Kang","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1590\/S0100-879X2004000700007","article-title":"Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: Similarity with polycystic ovary syndrome","volume":"37","author":"Baracat","year":"2004","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1210\/en.2007-1254","article-title":"Locus coeruleus mediates cold stress-induced polycystic ovary in rats","volume":"149","author":"Bernuci","year":"2008","journal-title":"Endocrinology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1289\/ehp.0901257","article-title":"Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats","volume":"118","author":"Fernandez","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_69","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_70","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_71","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1530\/JOE-15-0453","article-title":"Reproductive alterations in hyperinsulinemic but normoandrogenic msg obese female rats","volume":"229","author":"Gaspar","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1354\/vp.45-4-512","article-title":"Polycystic ovary syndrome with endometrial hyperplasia in a cynomolgus monkey (macaca fascicularis)","volume":"45","author":"Arifin","year":"2008","journal-title":"Vet. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1210\/js.2017-00305","article-title":"High-fat, high-sugar diet disrupts the preovulatory hormone surge and induces cystic ovaries in cycling female rats","volume":"1","author":"Volk","year":"2017","journal-title":"J. Endocr. Soc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1095\/biolreprod.116.142786","article-title":"High-fat high-sugar diet induces polycystic ovary syndrome in a rodent model","volume":"96","author":"Roberts","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1095\/biolreprod.114.120063","article-title":"High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome","volume":"91","author":"Lai","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/humrep\/dex338","article-title":"Chronic hyperandrogenemia in the presence and absence of a western-style diet impairs ovarian and uterine structure\/function in young adult rhesus monkeys","volume":"33","author":"Bishop","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.reprotox.2014.09.003","article-title":"Soy but not bisphenol a (bpa) induces hallmarks of polycystic ovary syndrome (PCOS) and related metabolic co-morbidities in rats","volume":"49","author":"Patisaul","year":"2014","journal-title":"Reprod. Toxicol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/00006254-196901000-00001","article-title":"Persistent estrus: An experimental model of the polycystic ovary syndrome","volume":"24","author":"Singh","year":"1969","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.fertnstert.2005.06.013","article-title":"Persistent estrus rat models of polycystic ovary disease: An update","volume":"84","author":"Singh","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1179\/147683009X423436","article-title":"Constant light induces alterations in melatonin levels, food intake, feed efficiency, visceral adiposity, and circadian rhythms in rats","volume":"12","author":"Wideman","year":"2009","journal-title":"Nutr. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1177\/0748730410361918","article-title":"Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female syrian hamsters","volume":"25","author":"Ansel","year":"2010","journal-title":"J. Biol. Rhythms"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1210\/endo-75-2-266","article-title":"Mediation of some effects of illumination on the rat estrous cycle by the sympathetic nervous system","volume":"75","author":"WURTMAN","year":"1964","journal-title":"Endocrinology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1096\/fj.12-210898","article-title":"Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity","volume":"27","author":"Coomans","year":"2013","journal-title":"FASEB J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1152\/ajplegacy.1966.210.5.1112","article-title":"Effect of light on corticosterone levels in plasma of rats","volume":"210","author":"Scheving","year":"1966","journal-title":"Am. J. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/j.1447-0756.2011.01705.x","article-title":"Stress-induced activation of ovarian heat shock protein 90 in a rat model of polycystic ovary syndrome","volume":"38","author":"Park","year":"2012","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1095\/biolreprod.102.008318","article-title":"Chronic intermittent cold stress activates ovarian sympathetic nerves and modifies ovarian follicular development in the rat","volume":"68","author":"Dorfman","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cmet.2010.05.012","article-title":"Adipose acyl-coa synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis","volume":"12","author":"Ellis","year":"2010","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1023\/A:1022417102206","article-title":"Establishment of the mimetic aging effect in mice caused by d-galactose","volume":"4","author":"Ho","year":"2003","journal-title":"Biogerontology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0047-6374(99)00022-6","article-title":"Advanced glycation in d-galactose induced mouse aging model","volume":"108","author":"Song","year":"1999","journal-title":"Mech. Ageing Dev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1126\/science.164.3880.719","article-title":"Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate","volume":"164","author":"Olney","year":"1969","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0014-4886(78)90050-X","article-title":"Hypothalamic lesion induced by injection of monosodium glutamate in suckling period and subsequent development of obesity","volume":"62","author":"Tanaka","year":"1978","journal-title":"Exp. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.toxlet.2017.12.029","article-title":"Neonatal exposure to bisphenol a alters the hypothalamic-pituitary-thyroid axis in female rats","volume":"285","author":"Fernandez","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1289\/ehp.01109675","article-title":"Perinatal exposure to low doses of bisphenol a affects body weight, patterns of estrous cyclicity, and plasma lh levels","volume":"109","author":"Rubin","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.taap.2017.01.021","article-title":"Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin\/leptin signaling in female rats","volume":"319","author":"Sena","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.peptides.2008.06.007","article-title":"Kiss-1\/kisspeptins and the metabolic control of reproduction: Physiologic roles and putative physiopathological implications","volume":"30","author":"Castellano","year":"2009","journal-title":"Peptides"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1210\/en.2010-1100","article-title":"Leptin deficiency and diet-induced obesity reduce hypothalamic kisspeptin expression in mice","volume":"152","author":"Quennell","year":"2011","journal-title":"Endocrinology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1095\/biolreprod.115.131631","article-title":"A novel letrozole model recapitulates both the reproductive and metabolic phenotypes of polycystic ovary syndrome in female mice","volume":"93","author":"Kauffman","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.fertnstert.2006.04.026","article-title":"Use of an aromatase inhibitor in patients with polycystic ovary syndrome: A prospective randomized trial","volume":"86","author":"Bayar","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/humupd\/dms003","article-title":"Aromatase inhibitors for PCOS: A systematic review and meta-analysis","volume":"18","author":"Misso","year":"2012","journal-title":"Hum. Reprod. Update"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/humrep\/deh690","article-title":"No evidence of mutations in the p450 aromatase gene in patients with polycystic ovary syndrome","volume":"20","author":"Soderlund","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1051\/rnd:2006003","article-title":"Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: A review","volume":"46","author":"Vanholder","year":"2006","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1292\/jvms.64.879","article-title":"Relationship among insulin-like growth factor-i, blood metabolites and postpartum ovarian function in dairy cows","volume":"64","author":"Zulu","year":"2002","journal-title":"J. Vet. Med. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jcpa.2009.11.002","article-title":"Insulin-like growth factor-ii and insulin-like growth factor-binding proteins in bovine cystic ovarian disease","volume":"142","author":"Rey","year":"2010","journal-title":"J. Comp. Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/rda.12311","article-title":"Gross pathology and endocrinology of ovarian cysts in bitches","volume":"49","author":"Knauf","year":"2014","journal-title":"Reprod. Domest. Anim."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.anireprosci.2010.06.001","article-title":"Relationships between ovarian cysts and morphological and hormonal state of ovarian cortex in sows","volume":"121","author":"Bielas","year":"2010","journal-title":"Anim. Reprod. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"356","DOI":"10.56093\/ijans.v85i4.47761","article-title":"Oxidative stress during cystic ovarian disease in water buffalo","volume":"85","author":"Jan","year":"2015","journal-title":"Indian J. Anim. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.anireprosci.2015.02.010","article-title":"Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease","volume":"156","author":"Hein","year":"2015","journal-title":"Anim. Reprod. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1530\/REP-06-0046","article-title":"Relationship between metabolic hormones and ovulation of dominant follicle during the first follicular wave post-partum in high-producing dairy cows","volume":"133","author":"Kawashima","year":"2007","journal-title":"Reproduction"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1439-0531.1993.tb01022.x","article-title":"Cystic degeneration in porcine ovaries-second communication: Concentrations of progesterone, estradiol-17\u03b2, and testosterone in cystic fluid and plasma; interpretation of the results","volume":"28","author":"Ebbert","year":"1993","journal-title":"Reprod. Domest. Anim."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2460\/javma.1992.201.01.107","article-title":"Follicular cystic ovaries and cystic endometrial hyperplasia in a bitch","volume":"201","author":"Durham","year":"1992","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2826.2006.01417.x","article-title":"Kiss-1 neurones are direct targets for leptin in the ob\/ob mouse","volume":"18","author":"Smith","year":"2006","journal-title":"J. Neuroendocrinol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"22693","DOI":"10.1073\/pnas.1012406108","article-title":"Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons","volume":"107","author":"Mayer","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1530\/ror.0.0040067","article-title":"Inhibitory effect of melatonin on gnrh-induced lh release","volume":"4","author":"Vanecek","year":"1999","journal-title":"Rev. Reprod."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/rep.1.00529","article-title":"Anti-mullerian hormone: A new marker for ovarian function","volume":"131","author":"Visser","year":"2006","journal-title":"Reproduction"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1093\/humrep\/deh873","article-title":"Serum anti-mullerian hormone levels during controlled ovarian hyperstimulation in women with polycystic ovaries with and without hyperandrogenism","volume":"20","author":"Margalioth","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/humrep\/deu076","article-title":"The role of amh in anovulation associated with PCOS: A hypothesis","volume":"29","author":"Homburg","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"E1649","DOI":"10.1210\/jc.2011-3133","article-title":"Differential regulation of ovarian anti-mullerian hormone (amh) by estradiol through alpha- and beta-estrogen receptors","volume":"97","author":"Grynberg","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1210\/endo-122-4-1592","article-title":"Adrenergic regulation of ovarian androgen biosynthesis is mediated via beta 2-adrenergic theca-interstitial cell recognition sites","volume":"122","author":"Hernandez","year":"1988","journal-title":"Endocrinology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1262\/jrd.17019","article-title":"Dexamethasone-induced changes in sympathetic innervation of porcine ovaries and in their steroidogenic activity","volume":"51","author":"Jana","year":"2005","journal-title":"J. Reprod. Dev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ctrv.2003.07.007","article-title":"Pi3k\/akt signalling pathway and cancer","volume":"30","author":"Casado","year":"2004","journal-title":"Cancer Treat. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1017\/S1462399411002109","article-title":"PI3K\/AKT, MAPK and AMPK signalling: Protein kinases in glucose homeostasis","volume":"14","author":"Schultze","year":"2012","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S1097-2765(04)00211-4","article-title":"The igf-1\/pi3k\/akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting foxo transcription factors","volume":"14","author":"Stitt","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2006.07.038","article-title":"Control of mammalian oocyte growth and early follicular development by the oocyte pi3 kinase pathway: New roles for an old timer","volume":"299","author":"Liu","year":"2006","journal-title":"Dev Biol"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1177\/1933719116667606","article-title":"Role of the pi3k-akt signaling pathway in the pathogenesis of polycystic ovary syndrome","volume":"24","author":"Li","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"25727","DOI":"10.1074\/jbc.M112.349902","article-title":"Involvement of the up-regulated foxo1 expression in follicular granulosa cell apoptosis induced by oxidative stress","volume":"287","author":"Shen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1677\/joe.0.1790195","article-title":"Relationship between foxo1 protein levels and follicular development, atresia, and luteinization in the rat ovary","volume":"179","author":"Shi","year":"2003","journal-title":"J. Endocrinol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.reprotox.2013.07.026","article-title":"High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression","volume":"42","author":"Nteeba","year":"2013","journal-title":"Reprod. Toxicol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bbrc.2004.04.185","article-title":"Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3K, AKT, IKK, and NF-kappaB","volume":"319","author":"Chandrasekar","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"L860","DOI":"10.1152\/ajplung.00131.2004","article-title":"Activation of pi3k-akt pathway mediates antiapoptotic effects of beta-adrenergic agonist in airway eosinophils","volume":"288","author":"Machida","year":"2005","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1210\/en.2003-0329","article-title":"Insulin augmentation of 17alpha-hydroxylase activity is mediated by phosphatidyl inositol 3-kinase but not extracellular signal-regulated kinase-1\/2 in human ovarian theca cells","volume":"145","author":"Munir","year":"2004","journal-title":"Endocrinology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00395-007-0691-y","article-title":"Metformin protects the ischemic heart by the akt-mediated inhibition of mitochondrial permeability transition pore opening","volume":"103","author":"Bhamra","year":"2008","journal-title":"Basic Res. Cardiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1158\/1078-0432.CCR-12-0662","article-title":"The PI3K\/AKT\/mTOR pathway as a therapeutic target in endometrial cancer","volume":"18","author":"Slomovitz","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0015-0282(01)01975-6","article-title":"Metformin directly inhibits androgen production in human thecal cells","volume":"76","author":"Attia","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_134","first-page":"CD003053","article-title":"Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, d-chiro-inositol) for polycystic ovary syndrome","volume":"2","author":"Lord","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/humupd\/dmm026","article-title":"The role of metformin in polycystic ovary syndrome: A systematic review","volume":"13","author":"Moll","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"11285","DOI":"10.1073\/pnas.1934283100","article-title":"Insulin-induced phosphorylation of fkhr (foxo1) targets to proteasomal degradation","volume":"100","author":"Matsuzaki","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased oxidative stress in obesity and its impact on metabolic syndrome","volume":"114","author":"Furukawa","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.bbrc.2009.08.106","article-title":"Free fatty acid-induced muscle insulin resistance and glucose uptake dysfunction: Evidence for pkc activation and oxidative stress-activated signaling pathways","volume":"389","author":"Ragheb","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1191\/0960327106ht621oa","article-title":"Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: Modulatory role of vitamin c, vitamin e and quercetin","volume":"25","author":"Farombi","year":"2006","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1126\/science.279.5350.537","article-title":"Catalytic galactose oxidase models: Biomimetic cu(ii)-phenoxyl-radical reactivity","volume":"279","author":"Wang","year":"1998","journal-title":"Science"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/nature04634","article-title":"Reactive oxygen species have a causal role in multiple forms of insulin resistance","volume":"440","author":"Houstis","year":"2006","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1172\/JCI10934","article-title":"Insulin\/igf-1 and tnf-alpha stimulate phosphorylation of irs-1 at inhibitory ser307 via distinct pathways","volume":"107","author":"Rui","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.biochi.2004.10.019","article-title":"Positive and negative regulation of insulin signaling through irs-1 phosphorylation","volume":"87","author":"Gual","year":"2005","journal-title":"Biochimie"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.biochi.2014.01.002","article-title":"Ffas-ros-erk\/p38 pathway plays a key role in adipocyte lipotoxicity on osteoblasts in co-culture","volume":"101","author":"Dong","year":"2014","journal-title":"Biochimie"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.freeradbiomed.2011.04.019","article-title":"Ros-activated p38 MAPK\/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation","volume":"51","author":"Wang","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.bbadis.2010.11.005","article-title":"Cyclic amp-mediated cyst expansion","volume":"1812","author":"Wallace","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1016\/j.febslet.2010.03.039","article-title":"Beta-2 adrenergic receptor mediated erk activation is regulated by interaction with magi-3","volume":"584","author":"Yang","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The ras-erk and pi3k-mtor pathways: Cross-talk and compensation","volume":"36","author":"Mendoza","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1038\/sj.onc.1210422","article-title":"Targeting the raf-mek-erk mitogen-activated protein kinase cascade for the treatment of cancer","volume":"26","author":"Roberts","year":"2007","journal-title":"Oncogene"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"10832","DOI":"10.1073\/pnas.170276797","article-title":"Modulation of akt kinase activity by binding to hsp90","volume":"97","author":"Sato","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1038\/sj.onc.1208548","article-title":"Hsp90-akt phosphorylates ask1 and inhibits ask1-mediated apoptosis","volume":"24","author":"Zhang","year":"2005","journal-title":"Oncogene"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/0006-291X(85)90494-2","article-title":"Synergistic stimulation of luteinizing hormone (LH) release by protein kinase c activators and ca2+-ionophore","volume":"130","author":"Naor","year":"1985","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/0002-9378(89)90321-9","article-title":"Differential role of protein kinase c in the action of luteinizing hormone-releasing hormone on hormone production in rat ovarian cells","volume":"160","author":"Wang","year":"1989","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/0006-291X(87)90737-6","article-title":"Role of protein kinase c in luteinizing hormone-releasing hormone (lhrh)-stimulated progesterone production in rat granulosa cells","volume":"146","author":"Wang","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1172\/JCI200422230","article-title":"Pkc-theta knockout mice are protected from fat-induced insulin resistance","volume":"114","author":"Kim","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/10408363.2011.596521","article-title":"Non-alcoholic fatty liver disease","volume":"48","author":"Smith","year":"2011","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/j.1365-2036.2011.04579.x","article-title":"Systematic review: Association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease","volume":"33","author":"Baranova","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.jhep.2007.04.012","article-title":"Nonalcoholic fatty liver disease in women with polycystic ovary syndrome","volume":"47","author":"Cerda","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.biocel.2008.10.027","article-title":"Non-alcoholic steatohepatitis and animal models: Understanding the human disease","volume":"41","author":"Embade","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1194\/jlr.M800042-JLR200","article-title":"Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet","volume":"49","author":"Rinella","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_161","first-page":"324","article-title":"Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome","volume":"8","author":"Liu","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1210\/jc.2017-02799","article-title":"Gut microbiota and the polycystic ovary syndrome (PCOS): Influence of sex, sex hormones and obesity","volume":"103","author":"Insenser","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.numecd.2012.02.007","article-title":"Gut\u2013liver axis: The impact of gut microbiota on non alcoholic fatty liver disease","volume":"22","author":"Compare","year":"2012","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1210\/en.2016-1317","article-title":"Neonatal androgen exposure causes persistent gut microbiota dysbiosis related to metabolic disease in adult female rats","volume":"157","author":"Tinahones","year":"2016","journal-title":"Endocrinology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00404-010-1401-9","article-title":"A comparative study on the outcomes of in vitro fertilization between women with polycystic ovary syndrome and those with sonographic polycystic ovary-only in gnrh antagonist cycles","volume":"282","author":"Kim","year":"2010","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S1016-8478(23)13725-3","article-title":"Expression of the mitochondrial atpase6 gene and tfam in down syndrome","volume":"15","author":"Lee","year":"2003","journal-title":"Mol. Cells"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Kim, Y.J., Kim, Y.Y., Shin, J.H., Kim, H., Ku, S.Y., and Suh, C.S. (2018). Variation in microrna expression profile of uterine leiomyoma with endometrial cavity distortion and endometrial cavity non-distortion. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092524"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s13770-018-0128-8","article-title":"The use of normal stem cells and cancer stem cells for potential anti-cancer therapeutic strategy","volume":"15","author":"Han","year":"2018","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s13770-018-0156-4","article-title":"Proliferation profile of uterine endometrial stromal cells during in vitro culture with gonadotropins: Recombinant versus urinary follicle stimulating hormone","volume":"16","author":"Kim","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s13770-018-0149-3","article-title":"Efficient production of murine uterine damage model","volume":"16","author":"Kim","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s13770-017-0051-4","article-title":"Differential microrna expression profile of human embryonic stem cell-derived cardiac lineage cells","volume":"14","author":"Kim","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s13770-016-0006-1","article-title":"Effects of estradiol on the paracrine regulator expression of in vitro maturated murine ovarian follicles","volume":"14","author":"Kim","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1111\/apt.14058","article-title":"Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease","volume":"45","author":"Kim","year":"2017","journal-title":"Aliment. Pharmacol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:55:41Z","timestamp":1760187341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,3]]},"references-count":173,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20112720"],"URL":"https:\/\/doi.org\/10.3390\/ijms20112720","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,3]]}}}