{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:59:46Z","timestamp":1788328786552,"version":"build-2803163510"},"reference-count":93,"publisher":"The Endocrine Society","issue":"8","funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD033852"],"award-info":[{"award-number":["R01HD033852"]}],"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":["U54HD3449"],"award-info":[{"award-number":["U54HD3449"]}],"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":["R01HD058300"],"award-info":[{"award-number":["R01HD058300"]}],"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":["R01HD083323"],"award-info":[{"award-number":["R01HD083323"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder of reproductive-age women involving overproduction of ovarian androgens and, in some cases, from the adrenal cortex. Family studies have established that PCOS is a complex heritable disorder with genetic and epigenetic components. Several small, noncoding RNAs (miRNAs) have been shown to be differentially expressed in ovarian cells and follicular fluid and in the circulation of women with PCOS. However, there are no reports of global miRNA expression and target gene analyses in ovarian theca cells isolated from normal cycling women and women with PCOS, which are key to the elucidation of the basis for the hyperandrogenemia characteristic of PCOS. With the use of small RNA deep sequencing (miR-seq), we identified 18 differentially expressed miRNAs in PCOS theca cells; of these, miR-130b-3p was predicted to target one of the PCOS genome-wide association study candidates, differentially expressed in neoplastic vs normal cells domain containing 1A (DENND1A). We previously reported that DENND1A variant 2 (DENND1A.V2), a truncated isoform of DENND1A, is upregulated in PCOS theca cells and mediates augmented androgen biosynthesis in PCOS theca cells. The comparison of miR-130b-3p in normal and PCOS theca cells demonstrated decreased miR-130b-3p expression in PCOS theca cells, which was correlated with increased DENND1A.V2, cytochrome P450 17\u03b1-hydroxylase (CYP17A1) mRNA and androgen biosynthesis. miR-130b-3p mimic studies established that increased miR130b-3p is correlated with decreased DENND1A.V2 and CYP17A1 expression. Thus, in addition to genetic factors, post-transcriptional regulatory mechanisms via miR-130b-3p underly androgen excess in PCOS. Ingenuity\u00ae Pathway Analysis Core Pathway and Network Analyses suggest a network by which miR-130b-3p, DENND1A, the luteinizing hormone\/choriogonadotropin receptor, Ras-related protein 5B, and signaling pathways that they potentially target may mediate hyperandrogenism in PCOS.<\/jats:p>","DOI":"10.1210\/en.2019-00013","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T09:09:43Z","timestamp":1560244183000},"page":"1964-1981","source":"Crossref","is-referenced-by-count":45,"title":["miRNA Profiling Reveals miRNA-130b-3p Mediates DENND1A Variant 2 Expression and Androgen Biosynthesis"],"prefix":"10.1210","volume":"160","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-2801","authenticated-orcid":false,"given":"Jan M","family":"McAllister","sequence":"first","affiliation":[{"name":"Department of Pathology, Pennsylvania State College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela X","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pennsylvania State College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-2847","authenticated-orcid":false,"given":"Bhavi P","family":"Modi","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7035-2202","authenticated-orcid":false,"given":"Maria E","family":"Teves","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-1570","authenticated-orcid":false,"given":"Grace R","family":"Mavodza","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pennsylvania State College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary L","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pennsylvania State College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsaiwei","family":"Shen","sequence":"additional","affiliation":[{"name":"LC Sciences, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-5674","authenticated-orcid":false,"given":"Lane K","family":"Christenson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-5781","authenticated-orcid":false,"given":"Kellie J","family":"Archer","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Ohio State University, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-0480","authenticated-orcid":false,"suffix":"III","given":"Jerome F","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia"},{"name":"Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,6,11]]},"reference":[{"issue":"5","key":"2019072416102445700_bib1","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1016\/j.fertnstert.2010.09.032","article-title":"Polycystic ovary syndrome: an ancient disorder","volume":"95","author":"Azziz","year":"2011","journal-title":"Fertil Steril"},{"issue":"9","key":"2019072416102445700_bib2","first-page":"3078","article-title":"Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study","volume":"83","author":"Knochenhauer","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2019072416102445700_bib3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nrendo.2011.227","article-title":"Polycystic ovary syndrome in 2011: genes, aging and sleep apnea in polycystic ovary syndrome","volume":"8","author":"Dunaif","year":"2011","journal-title":"Nat Rev Endocrinol"},{"issue":"12","key":"2019072416102445700_bib4","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1210\/jc.2013-2350","article-title":"Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline","volume":"98","author":"Legro","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2019072416102445700_bib5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nrendo.2015.230","article-title":"PCOS in 2015: new insights into the genetics of polycystic ovary syndrome [published correction appears in Nat Rev Endocrinol. 2016;12(3):183]","volume":"12","author":"Azziz","year":"2016","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"2019072416102445700_bib6","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"},{"issue":"1","key":"2019072416102445700_bib7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.fertnstert.2016.05.009","article-title":"Introduction: determinants of polycystic ovary syndrome","volume":"106","author":"Azziz","year":"2016","journal-title":"Fertil Steril"},{"issue":"6","key":"2019072416102445700_bib8","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1210\/er.2011-1034","article-title":"Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications","volume":"33","author":"Diamanti-Kandarakis","year":"2012","journal-title":"Endocr Rev"},{"key":"2019072416102445700_bib9","doi-asserted-by":"crossref","first-page":"a2968","DOI":"10.1136\/bmj.a2968","article-title":"Defining polycystic ovary syndrome","volume":"338","author":"Balen","year":"2009","journal-title":"BMJ"},{"issue":"3","key":"2019072416102445700_bib10","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.fertnstert.2013.11.027","article-title":"Hyperandrogenemia is implicated in both the metabolic and reproductive morbidities of polycystic ovary syndrome","volume":"101","author":"Sung","year":"2014","journal-title":"Fertil Steril"},{"issue":"4","key":"2019072416102445700_bib11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/humupd\/dmq001","article-title":"Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis","volume":"16","author":"Moran","year":"2010","journal-title":"Hum Reprod Update"},{"issue":"25","key":"2019072416102445700_bib12","doi-asserted-by":"crossref","first-page":"14956","DOI":"10.1073\/pnas.95.25.14956","article-title":"Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome","volume":"95","author":"Legro","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"2019072416102445700_bib13","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0015-0282(02)03275-2","article-title":"Molecular progress in infertility: polycystic ovary syndrome","volume":"78","author":"Legro","year":"2002","journal-title":"Fertil Steril"},{"issue":"1","key":"2019072416102445700_bib14","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12020-016-0878-9","article-title":"Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome","volume":"53","author":"Jiang","year":"2016","journal-title":"Endocrine"},{"issue":"12","key":"2019072416102445700_bib15","doi-asserted-by":"crossref","first-page":"E2754","DOI":"10.1210\/jc.2013-4435","article-title":"The expression of the miR-25\/93\/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome","volume":"99","author":"Wu","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2019072416102445700_bib16","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.bbrc.2016.12.059","article-title":"Deregulation of RUNX2 by miR-320a deficiency impairs steroidogenesis in cumulus granulosa cells from polycystic ovary syndrome (PCOS) patients","volume":"482","author":"Zhang","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"2019072416102445700_bib17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/bs.acc.2015.06.001","article-title":"Polycystic ovary syndrome-epigenetic mechanisms and aberrant microRNA","volume":"71","author":"Ilie","year":"2015","journal-title":"Adv Clin Chem"},{"issue":"19","key":"2019072416102445700_bib18","doi-asserted-by":"crossref","first-page":"27899","DOI":"10.18632\/oncotarget.8544","article-title":"Comprehensive analysis of genome-wide DNA methylation across human polycystic ovary syndrome ovary granulosa cell","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"2019072416102445700_bib19","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.fertnstert.2015.04.005","article-title":"Genome-wide screen of ovary-specific DNA methylation in polycystic ovary syndrome","volume":"104","author":"Yu","year":"2015","journal-title":"Fertil Steril"},{"issue":"9","key":"2019072416102445700_bib20","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1210\/jc.2008-0369","article-title":"Ovarian morphology is a marker of heritable biochemical traits in sisters with polycystic ovaries","volume":"93","author":"Franks","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2019072416102445700_bib21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJM199207163270304","article-title":"Detection of functional ovarian hyperandrogenism in women with androgen excess","volume":"327","author":"Ehrmann","year":"1992","journal-title":"N Engl J Med"},{"issue":"3","key":"2019072416102445700_bib22","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1210\/er.16.3.322","article-title":"Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion","volume":"16","author":"Ehrmann","year":"1995","journal-title":"Endocr Rev"},{"issue":"12","key":"2019072416102445700_bib23","doi-asserted-by":"crossref","first-page":"5925","DOI":"10.1210\/jcem.86.12.8088","article-title":"The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome","volume":"86","author":"Nelson","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2019072416102445700_bib24","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1210\/mend.13.6.0311","article-title":"Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries","volume":"13","author":"Nelson","year":"1999","journal-title":"Mol Endocrinol"},{"issue":"4","key":"2019072416102445700_bib25","first-page":"1158","article-title":"Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries","volume":"79","author":"Gilling-Smith","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2019072416102445700_bib26","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1093\/humrep\/12.8.1621","article-title":"Oestradiol feedback stimulation of androgen biosynthesis by human theca cells","volume":"12","author":"Gilling-Smith","year":"1997","journal-title":"Hum Reprod"},{"issue":"1","key":"2019072416102445700_bib27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1365-2265.1997.2321049.x","article-title":"Evidence for a primary abnormality in theca cell steroidogenesis in the polycystic ovarian syndrome","volume":"47","author":"Gilling-Smith","year":"1997","journal-title":"Clin Endocrinol"},{"issue":"2","key":"2019072416102445700_bib28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0950-351X(96)80057-7","article-title":"Hypersecretion of androgens by polycystic ovaries: the role of genetic factors in the regulation of cytochrome P450c17 alpha","volume":"10","author":"Franks","year":"1996","journal-title":"Baillieres Clin Endocrinol Metab"},{"issue":"1","key":"2019072416102445700_bib29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jri.2004.01.010","article-title":"The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling","volume":"63","author":"Wood","year":"2004","journal-title":"J Reprod Immunol"},{"issue":"29","key":"2019072416102445700_bib30","doi-asserted-by":"crossref","first-page":"26380","DOI":"10.1074\/jbc.M300688200","article-title":"The molecular phenotype of polycystic ovary syndrome (PCOS) theca cells and new candidate PCOS genes defined by microarray analysis","volume":"278","author":"Wood","year":"2003","journal-title":"J Biol Chem"},{"issue":"1","key":"2019072416102445700_bib31","doi-asserted-by":"crossref","first-page":"E182","DOI":"10.1210\/jc.2014-2689","article-title":"Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals","volume":"100","author":"Brower","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2019072416102445700_bib32","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"issue":"3","key":"2019072416102445700_bib33","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10815-013-0161-4","article-title":"Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome","volume":"31","author":"Roth","year":"2014","journal-title":"J Assist Reprod Genet"},{"issue":"7","key":"2019072416102445700_bib34","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1210\/jc.2013-1715","article-title":"Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo","volume":"98","author":"Sang","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2019072416102445700_bib35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/molehr\/gat051","article-title":"Differential expression of inflammation-related genes in the ovarian stroma and granulosa cells of PCOS women","volume":"20","author":"Schmidt","year":"2014","journal-title":"Mol Hum Reprod"},{"issue":"1","key":"2019072416102445700_bib36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1210\/en.2017-00219","article-title":"Functional characterization of microRNA-27a-3p expression in human polycystic ovary syndrome","volume":"159","author":"Wang","year":"2018","journal-title":"Endocrinology"},{"issue":"4","key":"2019072416102445700_bib37","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.fertnstert.2015.07.001","article-title":"Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro fertilization patients depending on their age and oocyte maturation stage","volume":"104","author":"Moreno","year":"2015","journal-title":"Fertil Steril"},{"issue":"1","key":"2019072416102445700_bib38","doi-asserted-by":"crossref","first-page":"14671","DOI":"10.1038\/s41598-017-13250-1","article-title":"Differential expression of miR-93 and miR-21 in granulosa cells and follicular fluid of polycystic ovary syndrome associating with different phenotypes","volume":"7","author":"Naji","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"2019072416102445700_bib39","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00404-017-4570-y","article-title":"Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular fluid, and serum of women with polycystic ovary syndrome (PCOS)","volume":"297","author":"Naji","year":"2018","journal-title":"Arch Gynecol Obstet"},{"issue":"6","key":"2019072416102445700_bib40","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1177\/1933719116673197","article-title":"microRNA-145 negatively regulates cell proliferation through targeting IRS1 in isolated ovarian Granulosa cells from patients with polycystic ovary syndrome","volume":"24","author":"Cai","year":"2017","journal-title":"Reprod Sci"},{"issue":"2","key":"2019072416102445700_bib41","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1159\/000491894","article-title":"microRNA-16 promotes ovarian granulosa cell proliferation and suppresses apoptosis through targeting PDCD4 in polycystic ovarian syndrome","volume":"48","author":"Fu","year":"2018","journal-title":"Cell Physiol Biochem"},{"issue":"1","key":"2019072416102445700_bib42","first-page":"281","article-title":"Bioinformatics identification of microRNAs involved in polycystic ovary syndrome based on microarray data","volume":"20","author":"Hou","year":"2019","journal-title":"Mol Med Rep"},{"key":"2019072416102445700_bib43","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.gene.2019.04.082","article-title":"The role of MiRNA in polycystic ovary syndrome (PCOS)","volume":"706","author":"Chen","year":"2019","journal-title":"Gene"},{"key":"2019072416102445700_bib44","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gene.2018.10.006","article-title":"miR-323-3p regulates the steroidogenesis and cell apoptosis in polycystic ovary syndrome (PCOS) by targeting IGF-1","volume":"683","author":"Wang","year":"2019","journal-title":"Gene"},{"key":"2019072416102445700_bib45","article-title":"Metformin regulates key microRNAs to improve endometrial receptivity through increasing implantation marker gene expression in patients with PCOS undergoing IVF\/ICSI [published online ahead of print 1 January 2019]","author":"Zhai","journal-title":"Reprod Sci"},{"issue":"1","key":"2019072416102445700_bib46","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/ncomms1859","article-title":"Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC","volume":"3","author":"Blandino","year":"2012","journal-title":"Nat Commun"},{"issue":"3","key":"2019072416102445700_bib47","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1159\/000464113","article-title":"The hippo signaling pathway regulates ovarian function via the proliferation of ovarian germline Stem cells","volume":"41","author":"Ye","year":"2017","journal-title":"Cell Physiol Biochem"},{"issue":"5","key":"2019072416102445700_bib48","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1210\/me.2003-0342","article-title":"GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1","volume":"18","author":"Fl\u00fcck","year":"2004","journal-title":"Mol Endocrinol"},{"issue":"3","key":"2019072416102445700_bib49","doi-asserted-by":"crossref","first-page":"684","DOI":"10.3390\/genes5030684","article-title":"microRNAs related to polycystic ovary syndrome (PCOS)","volume":"5","author":"S\u00f8rensen","year":"2014","journal-title":"Genes (Basel)"},{"issue":"10","key":"2019072416102445700_bib50","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1093\/molehr\/gax046","article-title":"The polycystic ovary syndrome-associated gene Yap1 is regulated by gonadotropins and sex steroid hormones in hyperandrogenism-induced oligo-ovulation in mouse","volume":"23","author":"Ji","year":"2017","journal-title":"Mol Hum Reprod"},{"issue":"2","key":"2019072416102445700_bib51","doi-asserted-by":"crossref","first-page":"169","DOI":"10.4103\/0366-6999.149189","article-title":"Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance","volume":"128","author":"Lin","year":"2015","journal-title":"Chin Med J (Engl)"},{"issue":"1","key":"2019072416102445700_bib52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ng.732","article-title":"Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3","volume":"43","author":"Chen","year":"2011","journal-title":"Nat Genet"},{"issue":"9","key":"2019072416102445700_bib53","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/ng.2384","article-title":"Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome","volume":"44","author":"Shi","year":"2012","journal-title":"Nat Genet"},{"issue":"1","key":"2019072416102445700_bib54","doi-asserted-by":"crossref","first-page":"8464","DOI":"10.1038\/ncomms9464","article-title":"Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome","volume":"6","author":"Day","year":"2015","journal-title":"Nat Commun"},{"issue":"1","key":"2019072416102445700_bib55","doi-asserted-by":"crossref","first-page":"7502","DOI":"10.1038\/ncomms8502","article-title":"Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations [published correction appears in Nat Commun. 2016;7(1):10762]","volume":"6","author":"Hayes","year":"2015","journal-title":"Nat Commun"},{"issue":"2","key":"2019072416102445700_bib56","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/humrep\/des424","article-title":"Genotype-phenotype correlations of PCOS susceptibility SNPs identified by GWAS in a large cohort of Han Chinese women","volume":"28","author":"Cui","year":"2013","journal-title":"Hum Reprod"},{"issue":"1","key":"2019072416102445700_bib57","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1038\/ncomms10762","article-title":"Corrigendum: genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations","volume":"7","author":"Hayes","year":"2016","journal-title":"Nat Commun"},{"issue":"2","key":"2019072416102445700_bib58","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1136\/jmedgenet-2011-100427","article-title":"Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts","volume":"49","author":"Goodarzi","year":"2012","journal-title":"J Med Genet"},{"issue":"1","key":"2019072416102445700_bib59","doi-asserted-by":"crossref","first-page":"e0168870","DOI":"10.1371\/journal.pone.0168870","article-title":"Phenotype and tissue expression as a function of genetic risk in polycystic ovary syndrome","volume":"12","author":"Pau","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"2019072416102445700_bib60","doi-asserted-by":"crossref","first-page":"e1007813","DOI":"10.1371\/journal.pgen.1007813","article-title":"Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria","volume":"14","author":"Day","year":"2018","journal-title":"PLoS Genet"},{"issue":"15","key":"2019072416102445700_bib61","doi-asserted-by":"crossref","first-page":"E1519","DOI":"10.1073\/pnas.1400574111","article-title":"Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype","volume":"111","author":"McAllister","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"2019072416102445700_bib62","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/BF02990066","article-title":"Functional, long-term human theca and granulosa cell cultures from polycystic ovaries","volume":"3","author":"McAllister","year":"1995","journal-title":"Endocrine"},{"issue":"2","key":"2019072416102445700_bib63","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1210\/me.2004-0178","article-title":"Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome","volume":"19","author":"Nelson-Degrave","year":"2005","journal-title":"Mol Endocrinol"},{"issue":"11","key":"2019072416102445700_bib64","doi-asserted-by":"crossref","first-page":"e48963","DOI":"10.1371\/journal.pone.0048963","article-title":"Cholesterol side-chain cleavage gene expression in theca cells: augmented transcriptional regulation and mRNA stability in polycystic ovary syndrome","volume":"7","author":"Wickenheisser","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"2019072416102445700_bib65","first-page":"2304","article-title":"Differential activity of the cytochrome P450 17alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells","volume":"85","author":"Wickenheisser","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2019072416102445700_bib66","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1196\/annals.1290.005","article-title":"Some new thoughts on the pathophysiology and genetics of polycystic ovary syndrome","volume":"997","author":"Strauss","year":"2003","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"2019072416102445700_bib67","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1210\/me.2003-0090","article-title":"Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1","volume":"18","author":"Wickenheisser","year":"2004","journal-title":"Mol Endocrinol"},{"issue":"2","key":"2019072416102445700_bib68","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1210\/en.2003-0940","article-title":"Valproate potentiates androgen biosynthesis in human ovarian theca cells","volume":"145","author":"Nelson-DeGrave","year":"2004","journal-title":"Endocrinology"},{"issue":"1","key":"2019072416102445700_bib69","first-page":"17","article-title":"Polycystic ovary syndrome (PCOS), diagnostic criteria, and AMH","volume":"18","author":"Bani Mohammad","year":"2017","journal-title":"Asian Pac J Cancer Prev"},{"key":"2019072416102445700_bib70","unstructured":"RRID:CVCL_0458, https:\/\/scicrunch.org\/resolver\/CVCL_0458."},{"key":"2019072416102445700_bib71","unstructured":"RRID:AB_2800459, https:\/\/scicrunch.org\/resolver\/AB_2800459."},{"key":"2019072416102445700_bib72","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2016.06.011","article-title":"Alternative splicing of DENND1A, a PCOS candidate gene, generates variant 2","volume":"434","author":"Tee","year":"2016","journal-title":"Mol Cell Endocrinol"},{"key":"2019072416102445700_bib73","unstructured":"RRID:AB_2092106, https:\/\/scicrunch.org\/resolver\/AB_2092106."},{"key":"2019072416102445700_bib74","unstructured":"RRID:AB_2800456, https:\/\/scicrunch.org\/resolver\/AB_2800456."},{"key":"2019072416102445700_bib75","unstructured":"RRID:AB_330978, https:\/\/scicrunch.org\/resolver\/AB_330978."},{"issue":"9","key":"2019072416102445700_bib76","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.1210\/jc.2002-020363","article-title":"Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients with PCOS: effects of serine kinase inhibitors and IR activators","volume":"87","author":"Li","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2019072416102445700_bib77","doi-asserted-by":"crossref","first-page":"6623","DOI":"10.1210\/jc.2005-0622","article-title":"Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2","volume":"90","author":"Urbanek","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2019072416102445700_bib78","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0015-0282(02)03153-9","article-title":"Self-selected women with polycystic ovary syndrome are reproductively and metabolically abnormal and undertreated","volume":"78","author":"Legro","year":"2002","journal-title":"Fertil Steril"},{"issue":"10","key":"2019072416102445700_bib79","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1210\/jc.2006-0951","article-title":"Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity","volume":"91","author":"Stewart","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2019072416102445700_bib80","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.fertnstert.2014.04.024","article-title":"Regulatory role of microRNAs in ovarian function","volume":"101","author":"Imbar","year":"2014","journal-title":"Fertil Steril"},{"issue":"6","key":"2019072416102445700_bib81","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1530\/REP-16-0071","article-title":"Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients: miRNA-509-3p promotes oestradiol secretion by targeting MAP3K8","volume":"151","author":"Huang","year":"2016","journal-title":"Reproduction"},{"issue":"4","key":"2019072416102445700_bib82","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1210\/jc.2015-3588","article-title":"microRNA species in follicular fluid associating with polycystic ovary syndrome and related intermediary phenotypes","volume":"101","author":"S\u00f8rensen","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2019072416102445700_bib83","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1159\/000373934","article-title":"Role of serum miRNAs in the prediction of ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients","volume":"35","author":"Zhao","year":"2015","journal-title":"Cell Physiol Biochem"},{"issue":"5","key":"2019072416102445700_bib84","doi-asserted-by":"crossref","first-page":"E729","DOI":"10.1210\/jc.2014-3827","article-title":"microRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome","volume":"100","author":"Jiang","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2019072416102445700_bib85","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.repbio.2017.09.005","article-title":"microRNA-27a-3p affects estradiol and androgen imbalance by targeting Creb1 in the granulosa cells in mouse polycytic ovary syndrome model","volume":"17","author":"Wang","year":"2017","journal-title":"Reprod Biol"},{"key":"2019072416102445700_bib86","doi-asserted-by":"crossref","DOI":"10.1530\/REP-18-0229","article-title":"miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS","author":"Yao","year":"2018","journal-title":"Reproduction"},{"issue":"26","key":"2019072416102445700_bib87","doi-asserted-by":"crossref","first-page":"18239","DOI":"10.1074\/jbc.M113.546044","article-title":"Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins","volume":"289","author":"Yin","year":"2014","journal-title":"J Biol Chem"},{"issue":"4","key":"2019072416102445700_bib88","first-page":"4889","article-title":"Inhibition of microRNA-19b promotes ovarian granulosa cell proliferation by targeting IGF-1 in polycystic ovary syndrome","volume":"17","author":"Zhong","year":"2018","journal-title":"Mol Med Rep"},{"issue":"1","key":"2019072416102445700_bib89","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13048-016-0298-8","article-title":"Circulatory microRNA 23a and microRNA 23b and polycystic ovary syndrome (PCOS): the effects of body mass index and sex hormones in an Eastern Han Chinese population","volume":"10","author":"Xiong","year":"2017","journal-title":"J Ovarian Res"},{"issue":"7","key":"2019072416102445700_bib90","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1016\/j.fertnstert.2009.01.069","article-title":"Aberration of blastocyst microRNA expression is associated with human infertility","volume":"93","author":"McCallie","year":"2010","journal-title":"Fertil Steril"},{"issue":"1","key":"2019072416102445700_bib91","doi-asserted-by":"crossref","first-page":"16890","DOI":"10.1038\/srep16890","article-title":"Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis","volume":"5","author":"Sathyapalan","year":"2015","journal-title":"Sci Rep"},{"key":"2019072416102445700_bib92","first-page":"28","article-title":"Consensus on women\u2019s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE\/ASRM-Sponsored 3rd PCOS Consensus Workshop Group","volume-title":"Fertil Steril","author":"Fauser","year":"2012"},{"issue":"7","key":"2019072416102445700_bib93","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.2337\/db12-0963","article-title":"miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance","volume":"62","author":"Chen","year":"2013","journal-title":"Diabetes"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/en.2019-00013\/28785115\/en.2019-00013.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/160\/8\/1964\/28996427\/en.2019-00013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T23:37:46Z","timestamp":1569281866000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/160\/8\/1964\/5512658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,11]]},"references-count":93,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2019-00013","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8]]},"published":{"date-parts":[[2019,6,11]]}}}