{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:34:01Z","timestamp":1793223241746,"version":"4.5.0"},"reference-count":114,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD071836"],"award-info":[{"award-number":["P50 HD071836"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21 HD102172"],"award-info":[{"award-number":["R21 HD102172"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD099096"],"award-info":[{"award-number":["R01 HD099096"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P01 HD44232"],"award-info":[{"award-number":["P01 HD44232"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001881"],"award-info":[{"award-number":["UL1TR001881"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008143","name":"Oregon National Primate Research Center","doi-asserted-by":"publisher","award":["P51 ODO11092"],"award-info":[{"award-number":["P51 ODO11092"]}],"id":[{"id":"10.13039\/100008143","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK121559"],"award-info":[{"award-number":["R01 DK121559"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wisconsin National Primate Research Center","award":["P51 OD011106"],"award-info":[{"award-number":["P51 OD011106"]}]},{"name":"Santa Monica Bay Woman\u2019s Club"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod Biol Endocrinol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.<\/jats:p>","DOI":"10.1186\/s12958-021-00878-y","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T10:03:20Z","timestamp":1641809000000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-1277","authenticated-orcid":false,"given":"Daniel A.","family":"Dumesic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasantha","family":"Padmanabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio D.","family":"Chazenbalk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Abbott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"878_CR1","first-page":"520","volume-title":"Yen and Jaffe\u2019s reproductive endocrinology: physiology, pathophysiology and clinical management","author":"RJ Chang","year":"2018","unstructured":"Chang RJ, Dumesic DA. Polycystic ovary syndrome and Hyperandrogenic states. In: Strauss III JF, Barbieri RL, editors. Yen and Jaffe\u2019s reproductive endocrinology: physiology, pathophysiology and clinical management. 8th ed. Philadelphia: Elsevier Saunders; 2018. p. 520\u201355.","edition":"8"},{"issue":"5","key":"878_CR2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1210\/er.2015-1018","volume":"36","author":"DA Dumesic","year":"2015","unstructured":"Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36(5):487\u2013525.","journal-title":"Endocr Rev"},{"issue":"4","key":"878_CR3","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/humupd\/dmq001","volume":"16","author":"LJ Moran","year":"2010","unstructured":"Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Repro Update. 2010;16(4):347\u201363.","journal-title":"Hum Repro Update"},{"issue":"1","key":"878_CR4","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/REP-19-0197","volume":"159","author":"DA Dumesic","year":"2019","unstructured":"Dumesic DA, Hoyos LR, Chazenbalk GD, Naik R, Padmanabhan V, Abbott DH. Mechanisms of intergenerational transmission of polycystic ovary syndrome. Reproduction. 2019;159(1):R1\u2013R13.","journal-title":"Reproduction"},{"issue":"2","key":"878_CR5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/17446651.2019.1576522","volume":"14","author":"DH Abbott","year":"2019","unstructured":"Abbott DH, Dumesic DA. Levine JE Hyperandrogenic origins of polycystic ovary syndrome \u2013 implications for pathophysiology and therapy. Expert Rev Endocrinol Metab. 2019;14(2):131\u201343.","journal-title":"Expert Rev Endocrinol Metab"},{"key":"878_CR6","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.1210\/jc.2018-00935","volume":"103","author":"E Nilsson","year":"2018","unstructured":"Nilsson E, Benrick A, Kokosar M, Krook A, Lindgren E, K\u00e4llman T, et al. Transcriptional and epigenetic changes influencing skeletal muscle metabolism in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2018;103:4465\u201377.","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"878_CR7","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1530\/REP-18-0449","volume":"158","author":"ER V\u00e1zquez-Mart\u00ednez","year":"2019","unstructured":"V\u00e1zquez-Mart\u00ednez ER, G\u00f3mez-Viais YI, Garc\u00eda-G\u00f3mez E, Reyes-Mayoral C, Reyes-Mu\u00f1oz E, Camacho-Arroyo I, et al. DNA methylation in the pathogenesis of polycystic ovary syndrome. Reproduction. 2019;158(1):R27\u201340.","journal-title":"Reproduction."},{"key":"878_CR8","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","volume":"33","author":"HJ Teede","year":"2018","unstructured":"Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Norman RJ on behalf of the international PCOS network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33:1602\u201318.","journal-title":"Hum Reprod"},{"key":"878_CR9","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1210\/jc.2008-0222","volume":"93","author":"JL Rosenzweig","year":"2008","unstructured":"Rosenzweig JL, Ferrannini E, Grundy SM, Haffner SM, Heine RJ, Horton ES, et al. Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:3671\u201389.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"878_CR10","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1210\/jc.2012-3115","volume":"98","author":"HR Wyatt","year":"2013","unstructured":"Wyatt HR. Update on treatment strategies for obesity. J Clin Endocrinol Metab. 2013;98(4):1299\u2013306.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"878_CR11","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/humupd\/dmg024","volume":"9","author":"R Pasquali","year":"2003","unstructured":"Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update. 2003;9(4):359\u201372.","journal-title":"Hum Reprod Update"},{"issue":"6","key":"878_CR12","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1210\/er.2011-1034","volume":"33","author":"E Diamanti-Kandarakis","year":"2012","unstructured":"Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endo Rev. 2012;33(6):981\u20131030.","journal-title":"Endo Rev"},{"key":"878_CR13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1467-789X.2012.01053.x","volume":"14","author":"SS Lim","year":"2013","unstructured":"Lim SS, Norman RJ, Davies MJ, Moran LJ. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obes Rev. 2013;14:95\u2013109.","journal-title":"Obes Rev"},{"issue":"1","key":"878_CR14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1210\/jc.2007-1834","volume":"93","author":"BO Yildiz","year":"2008","unstructured":"Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93(1):162\u20138.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"878_CR15","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/humupd\/dmy007","volume":"24","author":"NS Kakoly","year":"2018","unstructured":"Kakoly NS, Khomami MB, Joham AE, Corray SD, Misso ML, Norman RJ, et al. Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression. Hum Reprod Update. 2018;24(4):455\u201367.","journal-title":"Hum Reprod Update"},{"issue":"8","key":"878_CR16","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.2337\/diacare.25.8.1351","volume":"25","author":"LP Palaniappan","year":"2002","unstructured":"Palaniappan LP, Carnethon MR, Fortmann SP. Heterogeneity in the relationship between ethnicity, BMI, and fasting insulin. Diabetes Care. 2002;25(8):1351\u20137.","journal-title":"Diabetes Care"},{"key":"878_CR17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.coemr.2020.03.004","volume":"12","author":"S Mumusoglu","year":"2020","unstructured":"Mumusoglu S, Yidiz BO. Polycystic ovary syndrome phenotypes and prevalence: differential impact of diagnostic criteria and clinical versus unselected population. Curr Opin Endocr Metab Res. 2020;12:66\u201371.","journal-title":"Curr Opin Endocr Metab Res"},{"issue":"6","key":"878_CR18","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.fertnstert.2016.07.1121","volume":"106","author":"D Lizneva","year":"2016","unstructured":"Lizneva D, Kirubakaran R, Mykhalchenko K, Suturina L, Chernukha G, Diamond MP, et al. Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis. Fertil Steril. 2016;106(6):1510\u20131520.e2.","journal-title":"Fertil Steril"},{"issue":"4","key":"878_CR19","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1210\/jc.2017-00047","volume":"102","author":"E S\u00f8ndergaard","year":"2017","unstructured":"S\u00f8ndergaard E, Espinosa De Ycaza AE, Morgan-Bathke M, Jensen MD. How to measure adipose tissue insulin sensitivity. J Clin Endocrinol Metab. 2017;102(4):1193\u20139.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"878_CR20","doi-asserted-by":"crossref","first-page":"E1088","DOI":"10.1210\/jc.2013-1295","volume":"98","author":"U Ezeh","year":"2013","unstructured":"Ezeh U, Yildiz BO, Azziz R. Referral bias in defining the phenotype and prevalence of obesity in polycystic ovary syndrome. J Clin Endocrinol Metab. 2013;98(6):E1088\u201396.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"878_CR21","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1210\/jc.2016-1376","volume":"101","author":"K Hershkop","year":"2016","unstructured":"Hershkop K, Besor O, Santoro N, Pierpont B, Caprio S, Weiss R. Adipose insulin resistance in obese adolescents across the spectrum of glucose tolerance. J Clin Endocrinol Metab. 2016;101(6):2423\u201331.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"878_CR22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1003132","volume":"17","author":"M Dapas","year":"2020","unstructured":"Dapas M, Lin FTJ, Nadkarni GN, Sisk R, Legro RS, Urbanek M, et al. Distinct subtypes of polycystic ovary syndrome with novel genetic associations: an unsupervised, phenotypic clustering analysis. PLoS Med. 2020;17(6):e1003132.","journal-title":"PLoS Med"},{"issue":"1","key":"878_CR23","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s13148-020-00970-x","volume":"12","author":"KL Leung","year":"2020","unstructured":"Leung KL, Sanchita S, Pham CT, Davis BA, Okhovat M, Ding X, et al. Dynamic changes in chromatin accessibility, altered adipogenic gene expression, and total versus de novo fatty acid synthesis in subcutaneous adipose stem cells of normal-weight polycystic ovary syndrome (PCOS) women during adipogenesis: evidence of cellular programming. Clin Epigenetics. 2020;12(1):181. https:\/\/doi.org\/10.1186\/s13148-020-00970-x.","journal-title":"Clin Epigenetics."},{"issue":"11","key":"878_CR24","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1210\/jc.2016-2586","volume":"101","author":"DA Dumesic","year":"2016","unstructured":"Dumesic DA, Akopians AL, Madrigal VK, Ramirez E, Margolis DJ, Sarma MK, et al. Hyperandrogenism accompanies increased intra-abdominal fat storage in Normal weight polycystic ovary syndrome women. J Clin Endocrinol Metab. 2016;101(11):4178\u201388.","journal-title":"J Clin Endocrinol Metab"},{"key":"878_CR25","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1210\/jc.2014-2786","volume":"100","author":"F Tosi","year":"2015","unstructured":"Tosi F, Di Sarra D, Kaufman JM, Bonin C, Moretta R, Bonoro E, et al. Total body fat and central fat mass independently predict insulin resistance but not hyperandrogenemia in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015;100:661\u20139.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"878_CR26","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1210\/jc.2018-02086","volume":"104","author":"DA Dumesic","year":"2019","unstructured":"Dumesic DA, Phan JD, Leung KL, Grogan TR, Ding X, Li X, et al. Adipose insulin resistance in Normal-weight polycystic ovary syndrome women. J Clin Endocrinol Metab. 2019;104(6):2171\u201383.","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"878_CR27","first-page":"8","volume":"7","author":"J Holte","year":"1994","unstructured":"Holte J, Bergh T, Berne C, Berglund L, Lithell H. Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab. 1994;7(5):8 1052\u20138.","journal-title":"J Clin Endocrinol Metab"},{"key":"878_CR28","doi-asserted-by":"crossref","first-page":"E1756","DOI":"10.1210\/jc.2011-0615","volume":"96","author":"T McLaughlin","year":"2011","unstructured":"McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011;96:E1756\u201360.","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"878_CR29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1210\/jc.2005-1329","volume":"91","author":"DA Ehrmann","year":"2006","unstructured":"Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. PCOS\/Troglitazone study group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(1):48\u201353.","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"878_CR30","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.2337\/diacare.14.12.1132","volume":"14","author":"P Bjorntorp","year":"1991","unstructured":"Bjorntorp P. Metabolic implications of body fat distribution. Diabet Care. 1991;14(12):1132\u201343.","journal-title":"Diabet Care"},{"key":"878_CR31","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s00125-003-1324-0","volume":"47","author":"A Dicker","year":"2004","unstructured":"Dicker A, Ryden M, Naslund E, Muehlen IE, Wiren M, Lafontan M, et al. Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots. Diabetologia. 2004;47:420\u20138.","journal-title":"Diabetologia."},{"issue":"1","key":"878_CR32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.biochi.2004.11.012","volume":"87","author":"P Arner","year":"2005","unstructured":"Arner P. Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome. Biochimie. 2005;87(1):39\u201343.","journal-title":"Biochimie."},{"issue":"2","key":"878_CR33","doi-asserted-by":"crossref","first-page":"484","DOI":"10.2337\/diabetes.51.2.484","volume":"51","author":"I Ek","year":"2002","unstructured":"Ek I, Arner P, Ryd\u00e9n M, Holm C, Th\u00f6rne A, Hoffstedt J, et al. A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes. 2002;51(2):484\u201392.","journal-title":"Diabetes."},{"issue":"9733","key":"878_CR34","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1016\/S0140-6736(10)60408-4","volume":"375","author":"VT Samuel","year":"2010","unstructured":"Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unraveling the mechanism. Lancet. 2010;375(9733):2267\u201377.","journal-title":"Lancet."},{"issue":"9","key":"878_CR35","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.steroids.2013.05.001","volume":"78","author":"GD Chazenbalk","year":"2013","unstructured":"Chazenbalk GD, Singh P, Irge D, Shah A, Abbott DH, Dumesic DA. Androgens inhibit adipogenesis during human adipose stem cell commitment to predipocyte formation. Steroids. 2013;78(9):920\u20136.","journal-title":"Steroids."},{"issue":"11","key":"878_CR36","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrm3198","volume":"12","author":"AG Cristancho","year":"2011","unstructured":"Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011;12(11):722\u201334.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"81","key":"878_CR37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-052110-115718","volume":"7","author":"QQ Tang","year":"2012","unstructured":"Tang QQ, Lane MD. Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem. 2012;7(81):715\u201336.","journal-title":"Annu Rev Biochem"},{"issue":"11","key":"878_CR38","doi-asserted-by":"crossref","first-page":"9453","DOI":"10.3390\/nu7115475","volume":"7","author":"C Saponaro","year":"2015","unstructured":"Saponaro C, Gaggini M, Carli F, Gastaldelli A. The subtle balance between lipolysis and lipogenesis: a critical point in metabolic homeostasis. Nutrients. 2015;7(11):9453\u201374.","journal-title":"Nutrients."},{"issue":"4","key":"878_CR39","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/apha.12246","volume":"210","author":"T Romacho","year":"2014","unstructured":"Romacho T, Elsen M, Rohrborn D, Eckel J. Adipose tissue and its role in organ crosstalk. Acta Physiol (Oxf). 2014;210(4):733\u201353.","journal-title":"Acta Physiol (Oxf)"},{"issue":"3","key":"878_CR40","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1677\/joe.1.07070","volume":"192","author":"A Corbould","year":"2007","unstructured":"Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol. 2007;192(3):585\u201394.","journal-title":"J Endocrinol"},{"issue":"2 Pt 1","key":"878_CR41","first-page":"E197","volume":"264","author":"D Rosenbaum","year":"1993","unstructured":"Rosenbaum D, Harber RS, Dunaif A. Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes. Am J Phys. 1993;264(2 Pt 1):E197\u2013202.","journal-title":"Am J Phys"},{"issue":"5","key":"878_CR42","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1210\/jc.2002-021573","volume":"88","author":"G Faulds","year":"2003","unstructured":"Faulds G, Ryd\u00e9n M, Ek I, Wahrenberg H, Arner P. Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. J Clin Endocrinol Metab. 2003;88(5):2269\u201373.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"878_CR43","first-page":"1147","volume":"82","author":"I Ek","year":"1997","unstructured":"Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H. Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab. 1997;82(4):1147\u201353.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"878_CR44","doi-asserted-by":"crossref","first-page":"E304","DOI":"10.1210\/jc.2010-1290","volume":"96","author":"L Manner\u00e5s-Holm","year":"2011","unstructured":"Manner\u00e5s-Holm L, Leonhardt H, Kullberg J, Jennische E, Od\u00e9n A, Holm G, et al. Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J Clin Endocrinol Metab. 2011;96(2):E304\u201311.","journal-title":"J Clin Endocrinol Metab"},{"issue":"1\u20132","key":"878_CR45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.mce.2008.10.035","volume":"301","author":"K Blouin","year":"2009","unstructured":"Blouin K, Veilleux A, Luu-The V, Tchernof A. Androgen metabolism in adipose tissue: recent advances. Mol Cell Endocrinol. 2009;301(1\u20132):97\u2013103.","journal-title":"Mol Cell Endocrinol"},{"issue":"2","key":"878_CR46","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1677\/joe.1.05762","volume":"183","author":"M Quinkler","year":"2004","unstructured":"Quinkler M, Sinha B, Tomlinson JW, Bujalska IJ, Stewart PM, Arlt W. Androgen generation in adipose tissue in women with simple obesity--a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5. J Endocrinol. 2004;183(2):331\u201342.","journal-title":"J Endocrinol"},{"issue":"9","key":"878_CR47","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1210\/jc.2017-00947","volume":"102","author":"MW O\u2019Reilly","year":"2017","unstructured":"O\u2019Reilly MW, Kempegowda P, Walsh M, Taylor AE, Manolopoulos KN, Allwood JW, et al. AKR1C3-mediated adipose androgen generation drives lipotoxicity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102(9):3327\u201339.","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"878_CR48","doi-asserted-by":"publisher","first-page":"bvab158","DOI":"10.1210\/jendso\/bvab158","volume":"5","author":"DA Dumesic","year":"2021","unstructured":"Dumesic DA, Tulberg A, McNamara M, Grogan TR, Abbott DH, Naik R, et al. Serum testosterone to Androstenedione ratio predicts metabolic health in Normal-weight polycystic ovary syndrome women. J Endocr Soc. 2021;5(11):bvab158. https:\/\/doi.org\/10.1210\/jendso\/bvab158.","journal-title":"J Endocr Soc"},{"issue":"7196","key":"878_CR49","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nature06902","volume":"453","author":"KL Spalding","year":"2008","unstructured":"Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783\u20137.","journal-title":"Nature."},{"issue":"7","key":"878_CR50","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.fertnstert.2018.08.042","volume":"110","author":"SC Fisch","year":"2018","unstructured":"Fisch SC, Farzan Nikou A, Wright EA, Phan JD, Leung KL, Grogan TR, et al. Precocious subcutaneous abdominal stem cell development to adipocytes in Normal-weight polycystic ovary syndrome women. Fertil Steril. 2018;110(7):1367\u201376.","journal-title":"Fertil Steril"},{"issue":"1","key":"878_CR51","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.fertnstert.2020.10.003","volume":"116","author":"DA Dumesic","year":"2021","unstructured":"Dumesic DA, Tulberg A, Leung KL, Fisch SC, Grogan TR, Abbott DH, et al. Accelerated subcutaneous abdominal stem cell adipogenesis predicts insulin sensitivity in normal-weight women with polycystic ovary syndrome. Fertil Steril. 2021;116(1):232\u201342.","journal-title":"Fertil Steril"},{"issue":"Pt Suppl 1","key":"878_CR52","doi-asserted-by":"publisher","first-page":"jeb164970","DOI":"10.1242\/jeb.164970","volume":"221","author":"P Tandon","year":"2018","unstructured":"Tandon P, Wafer R, Minchin JE. Adipose morphology and metabolic disease. J Expt Biol. 2018;221(Pt Suppl 1):jeb164970. https:\/\/doi.org\/10.1242\/jeb.164970.","journal-title":"J Expt Biol"},{"issue":"1","key":"878_CR53","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2337\/db09-0942","volume":"59","author":"E Arner","year":"2010","unstructured":"Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J, et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes. 2010;59(1):105\u20139.","journal-title":"Diabetes."},{"issue":"2","key":"878_CR54","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00125-017-4471-4","volume":"61","author":"M Longo","year":"2018","unstructured":"Longo M, Raciti GA, Zatterale F, Parrillo L, Desiderio A, Spinelli R, et al. Epigenetic modifications of the Zfp\/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity. Diabetologia. 2018;61(2):369\u201380.","journal-title":"Diabetologia."},{"issue":"7","key":"878_CR55","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1210\/en.2014-1050","volume":"155","author":"E Keller","year":"2014","unstructured":"Keller E, Chazenbalk GD, Aguilera P, Madrigal V, Grogan T, Elashoff D, et al. 2014. Impaired preadipocyte differentiation into adipocytes in subcutaneous abdominal adipose of PCOS-like female rhesus monkeys. Endocrinology. 2014;155(7):2696\u2013703.","journal-title":"Endocrinology."},{"issue":"5","key":"878_CR56","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1210\/en.2012-2145","volume":"154","author":"A Veiga-Lopez","year":"2013","unstructured":"Veiga-Lopez A, Moeller J, Patel D, Ye W, Pease A, Kinns J, et al. Developmental programming: impact of prenatal testosterone excess on insulin sensitivity, adiposity, and free fatty acid profile in postpubertal female sheep. Endocrinology. 2013;154(5):1731\u201342.","journal-title":"Endocrinology."},{"issue":"7","key":"878_CR57","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1177\/1933719117746767","volume":"25","author":"M Puttabyatappa","year":"2018","unstructured":"Puttabyatappa M, Lu C, Martin JD, Chazenbalk G, Dumesic D, Padmanabhan V. Developmental programming: impact of prenatal testosterone excess on steroidal machinery and cell differentiation markers in visceral adipocytes of female sheep. Reprod Sci. 2018;25(7):1010\u201323.","journal-title":"Reprod Sci"},{"issue":"2","key":"878_CR58","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1210\/en.2015-1565","volume":"157","author":"RC Cardoso","year":"2016","unstructured":"Cardoso RC, Veiga-Lopez A, Moeller J, Beckett E, Pease A, Keller E, et al. Developmental programming: impact of gestational steroid and metabolic milieus on adiposity and insulin sensitivity in prenatal testosterone-treated female sheep. Endocrinology. 2016;157(2):522\u201335.","journal-title":"Endocrinology."},{"issue":"6","key":"878_CR59","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.2337\/db18-1162","volume":"68","author":"J Nouws","year":"2019","unstructured":"Nouws J, Fitch M, Mata M, Santoro N, Galuppo B, Kursawe R, et al. Altered in vivo lipid fluxes and cell dynamics in subcutaneous adipose tissues are associated with the unfavorable pattern of fat distribution in obese adolescent girls. Diabetes. 2019;68(6):1168\u201377.","journal-title":"Diabetes."},{"issue":"4","key":"878_CR60","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41366-018-0227-6","volume":"43","author":"GR Umano","year":"2019","unstructured":"Umano GR, Shabanova V, Pierpont B, Mata M, Nouws J, Tric\u00f2 D, et al. A low visceral fat proportion, independent of total body fat mass, protects obese adolescent girls against fatty liver and glucose dysregulation: a longitudinal study. Int J Obes. 2019;43(4):673\u201382.","journal-title":"Int J Obes"},{"issue":"4","key":"878_CR61","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/OGX.0000000000000661","volume":"74","author":"KM Brennan","year":"2019","unstructured":"Brennan KM, Kroener LL, Chazenbalk GD, Dumesic DA. Polycystic ovary syndrome: impact of lipotoxicity on metabolic and reproductive health. Obstet Gynecol Surv. 2019;74(4):223\u201331.","journal-title":"Obstet Gynecol Surv"},{"issue":"9","key":"878_CR62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060237","volume":"6","author":"S Virtue","year":"2008","unstructured":"Virtue S, Vidal-Puig A. It's not how fat you are, it's what you do with it that counts. PLoS Biol. 2008;6(9):e237. https:\/\/doi.org\/10.1371\/journal.pbio.0060237.","journal-title":"PLoS Biol"},{"issue":"3","key":"878_CR63","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.bbalip.2009.10.006","volume":"1801","author":"RH Unger","year":"2010","unstructured":"Unger RH, Clark GO, Scherer PE, Orci L. Lipid homeostasis, lipotoxicity and the metabolic syndrome. Biochim Biophys Acta. 2010;1801(3):209\u201314.","journal-title":"Biochim Biophys Acta"},{"issue":"9","key":"878_CR64","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.tem.2009.06.003","volume":"20","author":"F de Zegher","year":"2009","unstructured":"de Zegher F, Lopez-Bermejo A, Ib\u00e1\u00f1ez L. Adipose tissue expandability and the early origins of PCOS. Trends Endocrinol Metab. 2009;20(9):418\u201323.","journal-title":"Trends Endocrinol Metab"},{"issue":"11","key":"878_CR65","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.14309\/ajg.0000000000000262","volume":"114","author":"R Ramkissoon","year":"2019","unstructured":"Ramkissoon R, Gardner TB. Pancreatic Steatosis: an emerging clinical entity. Am J Gastroenterol. 2019;114(11):1726\u201334.","journal-title":"Am J Gastroenterol"},{"issue":"23","key":"878_CR66","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1056\/NEJMra1011035","volume":"371","author":"GI Shulman","year":"2014","unstructured":"Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(23):1131\u201341.","journal-title":"N Engl J Med"},{"issue":"1\u20132","key":"878_CR67","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mce.2013.01.001","volume":"373","author":"S Corbett","year":"2013","unstructured":"Corbett S, Morin-Papunen L. Polycystic ovary syndrome and recent human evolution. Mol Cell Endocrinol. 2013;373(1\u20132):39\u201350.","journal-title":"Mol Cell Endocrinol"},{"key":"878_CR68","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.coemr.2020.02.011","volume":"12","author":"M Dapas","year":"2020","unstructured":"Dapas M, Dunaif A. The contribution of rare genetic variants to the pathogenesis of polycystic ovary syndrome. Curr Opin Endocr Metab Res. 2020;12:26\u201332.","journal-title":"Curr Opin Endocr Metab Res."},{"key":"878_CR69","doi-asserted-by":"crossref","first-page":"26565","DOI":"10.1038\/srep26565","volume":"6","author":"D Shriner","year":"2016","unstructured":"Shriner D, Tekola-Ayele F, Adeyemo A, Rotimi CN. Ancient human migration after out-of-Africa. Sci Rep. 2016;6:26565.","journal-title":"Sci Rep"},{"issue":"7637","key":"878_CR70","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nature21347","volume":"541","author":"R Nielsen","year":"2017","unstructured":"Nielsen R, Akey JM, Jakobsson M, Pritchard JK, Tishkoff S, Willerslev E. Tracing the peopling of the world through genomics. Nature. 2017;541(7637):302\u201310.","journal-title":"Nature."},{"issue":"12","key":"878_CR71","doi-asserted-by":"crossref","first-page":"e1007813","DOI":"10.1371\/journal.pgen.1007813","volume":"14","author":"F Day","year":"2018","unstructured":"Day F, Karaderi T, Jones MR, Meun C, He C, Drong A, et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet. 2018;14(12):e1007813.","journal-title":"PLoS Genet"},{"issue":"9","key":"878_CR72","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1210\/jc.2018-02496","volume":"104","author":"M Dapas","year":"2019","unstructured":"Dapas M, Sisk R, Legro RS, Urbanek M, Dunaif A, Hayes MG. Family-based quantitative trait meta-analysis implicates rare noncoding variants in DENND1A in polycystic ovary syndrome. J Clin Endocrinol Metab. 2019;104(9):3835\u201350.","journal-title":"J Clin Endocrinol Metab"},{"issue":"15","key":"878_CR73","doi-asserted-by":"crossref","first-page":"E1519","DOI":"10.1073\/pnas.1400574111","volume":"111","author":"JM McAllister","year":"2014","unstructured":"McAllister JM, Modi B, Miller BA, Biegler J, Bruggeman R, Legro RS, et al. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci U S A. 2014;111(15):E1519\u201327.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"878_CR74","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2016.06.011","volume":"434","author":"MK Tee","year":"2016","unstructured":"Tee MK, Speek M, Legeza B, Modi B, Teves ME, McAllister JM, et al. Alternative splicing of DENND1A, a PCOS candidate gene, generates variant 2. Mol Cell Endocrinol. 2016;434:25\u201335.","journal-title":"Mol Cell Endocrinol"},{"issue":"7","key":"878_CR75","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1210\/jc.2018-02178","volume":"104","author":"LK Gorsic","year":"2019","unstructured":"Gorsic LK, Dapas M, Legro RS, Hayes MG, Urbanek M. Functional genetic variation in the anti-M\u00fcllerian hormone pathway in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2019;104(7):2855\u201374.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"878_CR76","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000500689","volume":"109","author":"AL Barbotin","year":"2019","unstructured":"Barbotin AL, Peign\u00e9 M, Malone SA, Giacobini P. Emerging roles of anti-M\u00fcllerian hormone in hypothalamic-pituitary function. Neuroendocrinology. 2019;109(3):218\u201329.","journal-title":"Neuroendocrinology."},{"key":"878_CR77","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3389\/fendo.2020.00274","volume":"11","author":"Y Tian","year":"2020","unstructured":"Tian Y, Li J, Su S, Cao Y, Wang Z, Zhao S, et al. PCOS-GWAS susceptibility variants in THADA, INSR, TOX3, and DENND1A are associated with metabolic syndrome or insulin resistance in women with PCOS. Front Endocrinol (Lausanne). 2020;11:274.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"2","key":"878_CR78","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41591-020-0751-5","volume":"26","author":"Ruth KS, Day FR, Tyrrell J, Thompson DJ, Wood AR, Mahajan A, Beaumont RN, Wittemans L, Martin S, Busch AS, Erzurumluoglu AM, Hollis B, O'Mara TA; Endometrial Cancer Association Consortium, McCarthy MI, Langenberg C, Easton DF, Wareham NJ, Burgess S, Murray A, Ong KK, Frayling TM, Perry JRB","year":"2020","unstructured":"Ruth KS, Day FR, Tyrrell J, Thompson DJ, Wood AR, Mahajan A, Beaumont RN, Wittemans L, Martin S, Busch AS, Erzurumluoglu AM, Hollis B, O'Mara TA; Endometrial Cancer Association Consortium, McCarthy MI, Langenberg C, Easton DF, Wareham NJ, Burgess S, Murray A, Ong KK, Frayling TM, Perry JRB. Using human genetics to understand the disease impacts of testosterone in men and women. Nat Med. 2020;26(2):252\u20138.","journal-title":"Nat Med"},{"key":"878_CR79","volume-title":"Polycystic Ovary Syndrome","author":"DH Abbott","year":"2021","unstructured":"Abbott DH, Greinwald EP, Levine JE. Developmental origins of polycystic ovary syndrome: everything starts in utero. In: Diamanti-Kandarakis E, editor. Polycystic Ovary Syndrome: Elsevier Press; 2021. In press."},{"issue":"9","key":"878_CR80","doi-asserted-by":"crossref","first-page":"3654","DOI":"10.1210\/jc.2006-0641","volume":"91","author":"B Cole","year":"2006","unstructured":"Cole B, Hensinger K, Maciel GA, Chang RJ, Erickson GF. Human fetal ovary development involves the spatiotemporal expression of p450c17 protein. J Clin Endocrinol Metab. 2006;91(9):3654\u201361.","journal-title":"J Clin Endocrinol Metab"},{"issue":"1 Pt 1","key":"878_CR81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-3476(88)80520-1","volume":"113","author":"CM Poissonnet","year":"1988","unstructured":"Poissonnet CM, LaVelle M, Burdi AR. Growth and development of adipose tissue. J Pediatr. 1988;113(1 Pt 1):1\u20139.","journal-title":"J Pediatr"},{"issue":"4","key":"878_CR82","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1210\/endo-87-4-680","volume":"87","author":"JA Resko","year":"1970","unstructured":"Resko JA. Androgen secretion by the fetal and neonatal rhesus monkey. Endocrinology. 1970;87(4):680\u20137.","journal-title":"Endocrinology."},{"issue":"2","key":"878_CR83","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1095\/biolreprod28.2.505","volume":"28","author":"WE Ellinwood","year":"1983","unstructured":"Ellinwood WE, McClellan MC, Brenner RM, Resko JA. Estradiol synthesis by fetal monkey ovaries correlates with antral follicle formation. Biol Reprod. 1983;28(2):505\u201316.","journal-title":"Biol Reprod"},{"issue":"5","key":"878_CR84","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/0002-9378(86)90746-5","volume":"154","author":"RL Barbieri","year":"1986","unstructured":"Barbieri RL, Saltzman DH, Torday JS, Randall RW, Frigoletto FD, Ryan KJ. Elevated concentrations of the beta-subunit of human chorionic gonadotropin and testosterone in the amniotic fluid of gestations of diabetic mothers. Am J Obstet Gynecol. 1986;154(5):1039\u201343.","journal-title":"Am J Obstet Gynecol"},{"key":"878_CR85","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1001\/archpedi.1960.04020040820004","volume":"100","author":"SG Driscoll","year":"1960","unstructured":"Driscoll SG, Benirschke K, Curtis GW. Neonatal deaths among infants of diabetic mothers. Postmortem findings in ninety-five infants. Am J Dis Child. 1960;100:818\u201335.","journal-title":"Am J Dis Child"},{"key":"878_CR86","first-page":"1","volume":"241","author":"GT Hultquist","year":"1981","unstructured":"Hultquist GT, Olding LB. Endocrine pathology of infants of diabetic mothers. A quantitative morphological analysis including a comparison with infants of iso-immunized and of non-diabetic mothers. Acta Endocrinol Suppl (Copenh). 1981;241:1\u2013202.","journal-title":"Acta Endocrinol Suppl (Copenh)"},{"issue":"6","key":"878_CR87","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1111\/j.1365-2265.2012.04443.x","volume":"77","author":"S Palomba","year":"2012","unstructured":"Palomba S, Marotta R, Di Cello A, Russo T, Falbo A, Orio F, et al. Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study. Clin Endocrinol. 2012;77(6):898\u2013904.","journal-title":"Clin Endocrinol"},{"issue":"11","key":"878_CR88","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1210\/jc.2017-02764","volume":"103","author":"J Kent","year":"2018","unstructured":"Kent J, Dodson WC, Kunselman A, Pauli J, Stone A, Diamond MP, et al. Reproductive medicine network. Gestational weight gain in women with polycystic ovary syndrome: A controlled study. J Clin Endocrinol Metab. 2018;103(11):4315\u201323.","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"878_CR89","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1093\/humrep\/17.10.2573","volume":"17","author":"T Sir-Petermann","year":"2002","unstructured":"Sir-Petermann T, Maliqueo M, Angel B, Lara HE, P\u00e9rez-Bravo F, Recabarren SE. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod. 2002;17(10):2573\u20139.","journal-title":"Hum Reprod"},{"issue":"6","key":"878_CR90","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41591-018-0035-5","volume":"24","author":"B Tata","year":"2018","unstructured":"Tata B, Mimouni NEH, Barbotin AL, Malone SA, Loyens A, Pigny P, et al. Elevated prenatal anti-M\u00fcllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nat Med. 2018;24(6):834\u201346.","journal-title":"Nat Med"},{"key":"878_CR91","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.steroids.2014.06.005","volume":"88","author":"S Palomba","year":"2014","unstructured":"Palomba S, Falbo A, Chiossi G, Muscogiuri G, Fornaciari E, Orio F, et al. Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study. Steroids. 2014;88:36\u201343.","journal-title":"Steroids."},{"issue":"8","key":"878_CR92","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1210\/jc.2014-1214","volume":"99","author":"S Palomba","year":"2014","unstructured":"Palomba S, Falbo A, Chiossi G, Orio F, Tolino A, Colao A, et al. Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome: a prospective controlled clinical study. J Clin Endocrinol Metab. 2014;99(8):2942\u201351.","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"878_CR93","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1210\/jc.2009-0544","volume":"94","author":"M Hickey","year":"2009","unstructured":"Hickey M, Sloboda DM, Atkinson HC, Doherty DA, Franks S, Norman RJ, et al. The relationship between maternal and umbilical cord androgen levels and polycystic ovary syndrome in adolescence: a prospective cohort study. J Clin Endocrinol Metab. 2009;94(10):3714\u201320.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"878_CR94","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11154-007-9046-0","volume":"8","author":"DA Dumesic","year":"2007","unstructured":"Dumesic DA, Abbott DH, Padmanabhan V. Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord. 2007;8(2):127\u201341.","journal-title":"Rev Endocr Metab Disord"},{"issue":"3","key":"878_CR95","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-0034-1371087","volume":"32","author":"DA Dumesic","year":"2014","unstructured":"Dumesic DA, Goodarzi MO, Chazenbalk GD, Abbott DH. Intrauterine environment and polycystic ovary syndrome. Semin Reprod Med. 2014;32(3):159\u201365.","journal-title":"Semin Reprod Med"},{"issue":"5","key":"878_CR96","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/humupd\/dmv029","volume":"21","author":"S Palomba","year":"2015","unstructured":"Palomba S, de Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21(5):575\u201392.","journal-title":"Hum Reprod Update"},{"issue":"2","key":"878_CR97","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ejogrb.2012.10.015","volume":"166","author":"M Maliqueo","year":"2013","unstructured":"Maliqueo M, Lara HE, S\u00e1nchez F, Echibur\u00fa B, Crisosto N, Sir-Petermann T. Placental steroidogenesis in pregnant women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;166(2):151\u20135.","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"3","key":"878_CR98","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.cmet.2021.01.004","volume":"33","author":"NEH Mimouni","year":"2021","unstructured":"Mimouni NEH, Paiva I, Barbotin AL, Timzoura FE, Plassard D, Le Gras S, et al. Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process. Cell Metab. 2021;33(3):513\u2013530.e8.","journal-title":"Cell Metab"},{"issue":"4","key":"878_CR99","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1210\/endrev\/bnaa010","volume":"41","author":"E Stener-Victorin","year":"2020","unstructured":"Stener-Victorin E, Padmanabhan P, Walters KA, Campbell RE, Benrick A, Giacobini P, et al. Animal models to understand the etiology and pathophysiology of polycystic ovary syndrome. Endocr Rev. 2020;41(4):538\u201376.","journal-title":"Endocr Rev"},{"key":"878_CR100","first-page":"329","volume-title":"Developmental programming of ovarian dysfunction. Novel concepts in ovarian endocrinology","author":"V Padmanabhan","year":"2007","unstructured":"Padmanabhan V, Veiga-Lopez A, Abbott DH, Dumesic DA. In: Gonzalez-Bulnes A, editor. Developmental programming of ovarian dysfunction. Novel concepts in ovarian endocrinology. Kerala: Research Signpost; 2007. p. 329\u201352."},{"issue":"5","key":"878_CR101","doi-asserted-by":"crossref","first-page":"E741","DOI":"10.1152\/ajpendo.00058.2010","volume":"299","author":"DH Abbott","year":"2010","unstructured":"Abbott DH, Bruns CR, Barnett DK, Dunaif A, Goodfriend TL, Dumesic DA, et al. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring. Am J Physiol Endocrinol Metab. 2010;299(5):E741\u201351.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"6","key":"878_CR102","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1210\/en.2014-2006","volume":"156","author":"B Abi Salloum","year":"2015","unstructured":"Abi Salloum B, Veiga-Lopez A, Abbott DH, Burant CF, Padmanabhan V. Developmental programming: exposure to testosterone excess disrupts steroidal and metabolic environment in pregnant sheep. Endocrinology. 2015;156(6):2323\u201337.","journal-title":"Endocrinology."},{"issue":"2","key":"878_CR103","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1210\/en.2009-1015","volume":"151","author":"V Padmanabhan","year":"2010","unstructured":"Padmanabhan V, Veiga-Lopez A, Abbott DH, Recabarren SE, Herkimer C. Developmental programming: impact of prenatal testosterone excess and postnatal weight gain on insulin sensitivity index and transfer of traits to offspring of overweight females. Endocrinology. 2010;151(2):595\u2013605.","journal-title":"Endocrinology."},{"issue":"5","key":"878_CR104","doi-asserted-by":"crossref","first-page":"E801","DOI":"10.1152\/ajpendo.00107.2005","volume":"289","author":"SE Recabarren","year":"2005","unstructured":"Recabarren SE, Padmanabhan V, Codner E, Lobos A, Dur\u00e1n C, Vidal M, et al. Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone. Am J Physiol Endocrinol Metab. 2005;289(5):E801\u20136.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"6","key":"878_CR105","doi-asserted-by":"crossref","first-page":"E1837","DOI":"10.1152\/ajpendo.00668.2006","volume":"292","author":"AJ King","year":"2007","unstructured":"King AJ, Olivier NB, Mohankumar PS, Lee JS, Padmanabhan V, Fink GD. Hypertension caused by prenatal testosterone excess in female sheep. Am J Physiol Endocrinol Metab. 2007;292(6):E1837\u201341.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"4","key":"878_CR106","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/humrep\/dex036","volume":"32","author":"DH Abbott","year":"2017","unstructured":"Abbott DH, Rayome BH, Dumesic DA, Lewis KC, Edwards AK, Wallen K, et al. Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys. Hum Reprod. 2017;32(4):923\u201336.","journal-title":"Hum Reprod"},{"issue":"4","key":"878_CR107","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1354\/vp.45-4-512","volume":"45","author":"E Arifin","year":"2008","unstructured":"Arifin E, Shively CA, Register TC, Cline JM. Polycystic ovary syndrome with endometrial hyperplasia in a cynomolgus monkey (Macaca fascicularis). Vet Pathol. 2008;45(4):512\u20135.","journal-title":"Vet Pathol"},{"issue":"12","key":"878_CR108","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3390\/medsci7120107","volume":"7","author":"DH Abbott","year":"2019","unstructured":"Abbott DH, Rogers J, Dumesic DA, Levine JE. Naturally occurring and experimentally induced Rhesus macaque models for polycystic ovary syndrome: translational gateways to clinical application. Med Sci (Basel). 2019;7(12):107. https:\/\/doi.org\/10.3390\/medsci7120107.","journal-title":"Med Sci (Basel)"},{"issue":"5","key":"878_CR109","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrendo.2018.24","volume":"14","author":"HF Escobar-Morreale","year":"2018","unstructured":"Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018;14(5):270\u201384.","journal-title":"Nat Rev Endocrinol"},{"issue":"8","key":"878_CR110","doi-asserted-by":"crossref","first-page":"e2695","DOI":"10.1210\/clinem\/dgaa285","volume":"105","author":"H Cena","year":"2020","unstructured":"Cena H, Chiovato L, Nappi RE. Obesity, polycystic ovary syndrome, and infertility: A new avenue for GLP-1 receptor agonists. J Clin Endocrinol Metab. 2020;105(8):e2695\u2013709.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"878_CR111","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S2352-4642(18)30385-7","volume":"3","author":"LGE Hanem","year":"2019","unstructured":"Hanem LGE, Salvesen \u00d8, Juliusson PB, Carlsen SM, Nossum MCF, Vaage M\u00d8, et al. Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial. Lancet Child Adolesc Health. 2019;3(3):166\u201374.","journal-title":"Lancet Child Adolesc Health"},{"issue":"1","key":"878_CR112","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12958-017-0282-1","volume":"15","author":"R Homburg","year":"2017","unstructured":"Homburg R, Gudi A, Shah A, Layton M, A. A novel method to demonstrate that pregnant women with polycystic ovary syndrome hyper-expose their fetus to androgens as a possible stepping stone for the developmental theory of PCOS. A pilot study. Reprod Biol Endocrinol. 2017;15(1):61. https:\/\/doi.org\/10.1186\/s12958-017-0282-1.","journal-title":"Reprod Biol Endocrinol"},{"issue":"3","key":"878_CR113","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1017\/S2040174417001118","volume":"9","author":"ES Barrett","year":"2018","unstructured":"Barrett ES, Hoeger KM, Sathyanarayana S, Abbott DH, Redmon JB, Nguyen RHN, et al. Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure. J Dev Orig Health Dis. 2018;9(3):307\u201314.","journal-title":"J Dev Orig Health Dis"},{"issue":"8","key":"878_CR114","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1210\/jc.2005-2693","volume":"91","author":"T Sir-Petermann","year":"2006","unstructured":"Sir-Petermann T, Codner E, Maliqueo M, Echibur\u00fa B, Hitschfeld C, Crisosto N, et al. Increased anti-M\u00fcllerian hormone serum concentrations in prepubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(8):3105\u20139.","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Reproductive Biology and Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12958-021-00878-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12958-021-00878-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12958-021-00878-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T10:05:29Z","timestamp":1641809129000},"score":1,"resource":{"primary":{"URL":"https:\/\/rbej.biomedcentral.com\/articles\/10.1186\/s12958-021-00878-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,10]]},"references-count":114,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["878"],"URL":"https:\/\/doi.org\/10.1186\/s12958-021-00878-y","relation":{},"ISSN":["1477-7827"],"issn-type":[{"value":"1477-7827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,10]]},"assertion":[{"value":"20 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All studies were performed according to the Declaration of Helsinki after approval by the UCLA Institutional Review Board and signed informed consent by each subject (IRB number 12\u2013001780). The nonhuman primate studies were reviewed and approved by the Graduate School Animal Care and Use Committee of the University of Wisconsin, Madison and were performed consistent with the USDA Animal Welfare Act and regulations and the Guide for the Care and Use of Laboratory Animals. The animal care and use program at the University of Wisconsin maintains a Public Health Services Assurance, and is fully accredited by AAALAC. All sheep studies were conducted under approved protocols of Institutional Animal Care and Use Committee of the University of Michigan, which is fully accredited by AAALAC.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"D.A.D has consulted for Spruce Biosciences, Inc.; V.P., G.D.C. and D.H.A have nothing to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}