{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:46:09Z","timestamp":1790711169776,"version":"4.1.0"},"reference-count":128,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K15932"],"award-info":[{"award-number":["22K15932"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H00539"],"award-info":[{"award-number":["20H00539"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K19283"],"award-info":[{"award-number":["21K19283"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22ek0109464h0003"],"award-info":[{"award-number":["22ek0109464h0003"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["2022A-1"],"award-info":[{"award-number":["2022A-1"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["2023C-15"],"award-info":[{"award-number":["2023C-15"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["22K15932"],"award-info":[{"award-number":["22K15932"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["20H00539"],"award-info":[{"award-number":["20H00539"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["21K19283"],"award-info":[{"award-number":["21K19283"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["22ek0109464h0003"],"award-info":[{"award-number":["22ek0109464h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["2022A-1"],"award-info":[{"award-number":["2022A-1"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["2023C-15"],"award-info":[{"award-number":["2023C-15"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Takeda Science Foundation","award":["22K15932"],"award-info":[{"award-number":["22K15932"]}]},{"name":"Takeda Science Foundation","award":["20H00539"],"award-info":[{"award-number":["20H00539"]}]},{"name":"Takeda Science Foundation","award":["21K19283"],"award-info":[{"award-number":["21K19283"]}]},{"name":"Takeda Science Foundation","award":["22ek0109464h0003"],"award-info":[{"award-number":["22ek0109464h0003"]}]},{"name":"Takeda Science Foundation","award":["2022A-1"],"award-info":[{"award-number":["2022A-1"]}]},{"name":"Takeda Science Foundation","award":["2023C-15"],"award-info":[{"award-number":["2023C-15"]}]},{"DOI":"10.13039\/100007786","name":"National Center For Child Health and Development","doi-asserted-by":"publisher","award":["22K15932"],"award-info":[{"award-number":["22K15932"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center For Child Health and Development","doi-asserted-by":"publisher","award":["20H00539"],"award-info":[{"award-number":["20H00539"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center For Child Health and Development","doi-asserted-by":"publisher","award":["21K19283"],"award-info":[{"award-number":["21K19283"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center For Child Health and Development","doi-asserted-by":"publisher","award":["22ek0109464h0003"],"award-info":[{"award-number":["22ek0109464h0003"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center For Child Health and Development","doi-asserted-by":"publisher","award":["2022A-1"],"award-info":[{"award-number":["2022A-1"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center For Child Health and Development","doi-asserted-by":"publisher","award":["2023C-15"],"award-info":[{"award-number":["2023C-15"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders\/differences of sex development (DSD). To date, pathogenic variants of three nuclear receptor genes (NR5A1, NR0B1, and NR2F2) have been reported to cause DSD via atypical testicular development. In this review article, we describe the clinical significance of the NR5A1 variants as the cause of DSD and introduce novel findings from recent studies. NR5A1 variants are associated with 46,XY DSD and 46,XX testicular\/ovotesticular DSD. Notably, both 46,XX DSD and 46,XY DSD caused by the NR5A1 variants show remarkable phenotypic variability, to which digenic\/oligogenic inheritances potentially contribute. Additionally, we discuss the roles of NR0B1 and NR2F2 in the etiology of DSD. NR0B1 acts as an anti-testicular gene. Duplications containing NR0B1 result in 46,XY DSD, whereas deletions encompassing NR0B1 can underlie 46,XX testicular\/ovotesticular DSD. NR2F2 has recently been reported as a causative gene for 46,XX testicular\/ovotesticular DSD and possibly for 46,XY DSD, although the role of NR2F2 in gonadal development is unclear. The knowledge about these three nuclear receptors provides novel insights into the molecular networks involved in the gonadal development in human fetuses.<\/jats:p>","DOI":"10.3390\/biom13040691","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:25:11Z","timestamp":1681961111000},"page":"691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nuclear Receptor Gene Variants Underlying Disorders\/Differences of Sex Development through Abnormal Testicular Development"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1511-4820","authenticated-orcid":false,"given":"Atsushi","family":"Hattori","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"},{"name":"Division of Diversity Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-4035","authenticated-orcid":false,"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"},{"name":"Division of Diversity Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"902082","DOI":"10.3389\/fcell.2022.902082","article-title":"Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models","volume":"10","year":"2022","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1542\/peds.2006-0738","article-title":"International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology Consensus Statement on Management of Intersex Disorders. International Consensus Conference on Intersex","volume":"118","author":"Lee","year":"2006","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3389\/fendo.2020.00211","article-title":"Male Hypogonadism and Disorders of Sex Development","volume":"11","author":"Grinspon","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41576-021-00365-5","article-title":"Towards Improved Genetic Diagnosis of Human Differences of Sex Development","volume":"22","author":"Vilain","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1159\/000521381","article-title":"Monogenic Forms of DSD: An Update","volume":"96","author":"McElreavey","year":"2023","journal-title":"Horm. Res. Paediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101633","DOI":"10.1016\/j.beem.2022.101633","article-title":"Genetics of 46,XY Gonadal Dysgenesis","volume":"36","author":"Elzaiat","year":"2022","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jfma.2012.02.009","article-title":"Cytogenic and Molecular Analyses of 46,XX Male Syndrome with Clinical Comparison to Other Groups with Testicular Azoospermia of Genetic Origin","volume":"112","author":"Chiang","year":"2013","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1136\/jmedgenet-2016-104128","article-title":"Female-to-Male Sex Reversal Associated with Unique Xp21.2 Deletion Disrupting Genomic Regulatory Architecture of the Dosage-Sensitive Sex Reversal Region","volume":"54","author":"Dangle","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1210\/js.2019-00241","article-title":"The Natural History of a Man With Ovotesticular 46,XX DSD Caused by a Novel 3-Mb 15q26.2 Deletion Containing NR2F2 Gene","volume":"3","author":"Carvalheira","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/ajmg.a.38109","article-title":"22q11.2q13 Duplication Including SOX10 Causes Sex-Reversal and Peripheral Demyelinating Neuropathy, Central Dysmyelinating Leukodystrophy, Waardenburg Syndrome, and Hirschsprung Disease","volume":"173","author":"Falah","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ajhg.2018.01.021","article-title":"Loss of Function of the Nuclear Receptor NR2F2, Encoding COUP-TF2, Causes Testis Development and Cardiac Defects in 46,XX Children","volume":"102","author":"Bashamboo","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1093\/hmg\/ddw186","article-title":"A Recurrent p.Arg92Trp Variant in Steroidogenic Factor-1 (NR5A1) Can Act as a Molecular Switch in Human Sex Development","volume":"25","author":"Bashamboo","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/gim.2016.118","article-title":"NR5A1 Is a Novel Disease Gene for 46,XX Testicular and Ovotesticular Disorders of Sex Development","volume":"19","author":"Baetens","year":"2017","journal-title":"Genet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/humu.23116","article-title":"Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues","volume":"38","author":"Igarashi","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1002\/ajmg.a.62063","article-title":"Identification of the First Promoter-Specific Gain-of-Function SOX9 Missense Variant (p.E50K) in a Patient with 46,XX Ovotesticular Disorder of Sex Development","volume":"185","author":"Ushijima","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41431-021-00812-1","article-title":"Novel Variants in the Stem Cell Niche Factor WNT2B Define the Disease Phenotype as a Congenital Enteropathy with Ocular Dysgenesis","volume":"29","author":"Zhang","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.ajhg.2009.03.016","article-title":"Ovaries and Female Phenotype in a Girl with 46,XY Karyotype and Mutations in the CBX2 Gene","volume":"84","author":"Konrad","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1093\/hmg\/5.10.1625","article-title":"A Novel Germ Line Mutation in SOX9 Causes Familial Campomelic Dysplasia and Sex Reversal","volume":"5","author":"Cameron","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1530\/EJE-12-0136","article-title":"Partial Deletion of DMRT1 Causes 46,XY Ovotesticular Disorder of Sexual Development","volume":"167","author":"Ledig","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Xie, Y., Wu, C., Li, Z., Wu, Z., and Hong, L. (2022). Early Gonadal Development and Sex Determination in Mammal. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147500"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000363608","article-title":"Gonadal Development","volume":"27","author":"Bashamboo","year":"2014","journal-title":"Endocr. Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/bdrc.20142","article-title":"Gonocytes, the Forgotten Cells of the Germ Cell Lineage","volume":"87","author":"Culty","year":"2009","journal-title":"Birth Defects Res. Part C Embryo Today Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0925-4773(99)00123-9","article-title":"Expression of Steroidogenic Factor 1 and Wilms\u2019 Tumour 1 during Early Human Gonadal Development and Sex Determination","volume":"87","author":"Hanley","year":"1999","journal-title":"Mech. Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.diff.2022.03.002","article-title":"Development of the Human Fetal Testis: Morphology and Expression of Cellular Differentiation Markers","volume":"129","author":"Li","year":"2023","journal-title":"Differentiation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0925-4773(99)00307-X","article-title":"SRY, SOX9, and DAX1 Expression Patterns during Human Sex Determination and Gonadal Development","volume":"91","author":"Hanley","year":"2000","journal-title":"Mech. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1093\/humrep\/deu124","article-title":"Expression Patterns of DLK1 and INSL3 Identify Stages of Leydig Cell Differentiation during Normal Development and in Testicular Pathologies, Including Testicular Cancer and Klinefelter Syndrome","volume":"29","author":"Lottrup","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.stem.2020.12.004","article-title":"Single-Cell Analysis of the Developing Human Testis Reveals Somatic Niche Cell Specification and Fetal Germline Stem Cell Establishment","volume":"28","author":"Guo","year":"2021","journal-title":"Cell. Stem Cell."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-90-481-9069-0_6","article-title":"Nuclear Receptors: Small Molecule Sensors That Coordinate Growth, Metabolism and Reproduction","volume":"52","author":"Pardee","year":"2011","journal-title":"Subcell. Biochem."},{"key":"ref_29","first-page":"689","article-title":"Orphan Nuclear Receptors: From Gene to Function","volume":"20","year":"1999","journal-title":"Endocr. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1152\/physrev.00019.2018","article-title":"The Orphan Nuclear Receptors Steroidogenic Factor-1 and Liver Receptor Homolog-1: Structure, Regulation, and Essential Roles in Mammalian Reproduction","volume":"99","author":"Meinsohn","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"756","DOI":"10.3803\/EnM.2020.402","article-title":"Coordination of Multiple Cellular Processes by NR5A1\/Nr5a1","volume":"35","author":"Morohashi","year":"2020","journal-title":"Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/0092-8674(94)90211-9","article-title":"A Cell-Specific Nuclear Receptor Is Essential for Adrenal and Gonadal Development and Sexual Differentiation","volume":"77","author":"Luo","year":"1994","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nature06944","article-title":"Sex Determination Involves Synergistic Action of SRY and SF1 on a Specific Sox9 Enhancer","volume":"453","author":"Sekido","year":"2008","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/9629","article-title":"A Mutation in the Gene Encoding Steroidogenic Factor-1 Causes XY Sex Reversal and Adrenal Failure in Humans","volume":"22","author":"Achermann","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s13059-016-1105-y","article-title":"Disorders of Sex Development: Insights from Targeted Gene Sequencing of a Large International Patient Cohort","volume":"17","author":"Eggers","year":"2016","journal-title":"Genome Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1210\/js.2019-00306","article-title":"Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD","volume":"3","author":"Buonocore","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1530\/EC-18-0376","article-title":"Next Generation Sequencing (NGS) to Improve the Diagnosis and Management of Patients with Disorders of Sex Development (DSD)","volume":"8","author":"Hughes","year":"2019","journal-title":"Endocr. Connect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4103\/aja.aja_36_20","article-title":"Prevalence of Gene Mutations in a Chinese 46,XY Disorders of Sex Development Cohort Detected by Targeted next-Generation Sequencing","volume":"23","author":"Yu","year":"2021","journal-title":"Asian J. Androl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104154","DOI":"10.1016\/j.ejmg.2021.104154","article-title":"A Large Cohort of Disorders of Sex Development and Their Genetic Characteristics: 6 Novel Mutations in Known Genes","volume":"64","author":"Ata","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"810782","DOI":"10.3389\/fendo.2022.810782","article-title":"Disorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic Findings","volume":"13","author":"Globa","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1797","DOI":"10.1210\/clinem\/dgac064","article-title":"Contribution of Clinical and Genetic Approaches for Diagnosing 209 Index Cases With 46,XY Differences of Sex Development","volume":"107","author":"Gomes","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1007\/s11033-019-04980-8","article-title":"The Importance of the Multiplex Ligation-Dependent Probe Amplification in the Identification of a Novel Two-Exon Deletion of the NR5A1 Gene in a Patient with 46,XY Differences of Sex Development","volume":"46","author":"Nagy","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111570","DOI":"10.1016\/j.mce.2022.111570","article-title":"Whole Exome Sequencing Reveals Copy Number Variants in Individuals with Disorders of Sex Development","volume":"546","author":"Sreenivasan","year":"2022","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1210\/jcem.87.4.8376","article-title":"Gonadal Determination and Adrenal Development Are Regulated by the Orphan Nuclear Receptor Steroidogenic Factor-1, in a Dose-Dependent Manner","volume":"87","author":"Achermann","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.beem.2015.07.004","article-title":"DAX-1 (NR0B1) and Steroidogenic Factor-1 (SF-1, NR5A1) in Human Disease","volume":"29","author":"Suntharalingham","year":"2015","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1186\/s13023-021-02039-1","article-title":"One Hundred Twelve Cases of 46, XY DSD Patients after Initial Gender Assignment: A Short-Term Survey of Gender Role and Gender Dysphoria","volume":"16","author":"Hou","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e13585","DOI":"10.1111\/and.13585","article-title":"A Missense Mutation in NR5A1 Causing Female to Male Sex Reversal: A Case Report","volume":"52","author":"Askari","year":"2020","journal-title":"Andrologia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/bdrc.21145","article-title":"Wide Spectrum of NR5A1-Related Phenotypes in 46,XY and 46,XX Individuals","volume":"108","author":"Domenice","year":"2016","journal-title":"Birth Defects Res. Part C Embryo Today Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/humu.23672","article-title":"NR5A1 Gene Variants Repress the Ovarian-Specific WNT Signaling Pathway in 46,XX Disorders of Sex Development Patients","volume":"40","author":"Knarston","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1159\/000485868","article-title":"Phenotypic Variation in 46,XX Disorders of Sex Development Due to the NR5A1 p.R92W Variant: A Sibling Case Report and Literature Review","volume":"11","author":"Takasawa","year":"2017","journal-title":"Sex. Dev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000452888","article-title":"A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant","volume":"87","author":"Swartz","year":"2017","journal-title":"Horm. Res. Paediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.3389\/fphar.2018.01224","article-title":"Phenotype and Molecular Characterizations of 30 Children From China With NR5A1 Mutations","volume":"9","author":"Song","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13293-016-0114-6","article-title":"The p.R92W Variant of NR5A1\/Nr5a1 Induces Testicular Development of 46,XX Gonads in Humans, but Not in Mice: Phenotypic Comparison of Human Patients and Mutation-Induced Mice","volume":"7","author":"Miyado","year":"2016","journal-title":"Biol. Sex. Differ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1242\/dev.120.10.2787","article-title":"Sex-Dependent Expression of a Transcription Factor, Ad4BP, Regulating Steroidogenic P-450 Genes in the Gonads during Prenatal and Postnatal Rat Development","volume":"120","author":"Hatano","year":"1994","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1096\/fj.13-246108","article-title":"FOXL2 Transcriptionally Represses Sf1 Expression by Antagonizing WT1 during Ovarian Development in Mice","volume":"28","author":"Takasawa","year":"2014","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/humu.23916","article-title":"Mutation Update for the NR5A1 Gene Involved in DSD and Infertility","volume":"41","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17008","DOI":"10.1038\/hgv.2017.8","article-title":"A Novel C-Terminal Truncating NR5A1 Mutation in Dizygotic Twins","volume":"4","author":"Hattori","year":"2017","journal-title":"Hum. Genome Var."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Camats, N., Fl\u00fcck, C.E., and Aud\u00ed, L. (2020). Oligogenic Origin of Differences of Sex Development in Humans. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051809"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kouri, C., Sommer, G., and Fl\u00fcck, C.E. (2021). Oligogenic Causes of Human Differences of Sex Development: Facing the Challenge of Genetic Complexity. Horm. Res. Paediatr., online ahead of print.","DOI":"10.1159\/000519691"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1002\/ajmg.a.62129","article-title":"Advances in Genomic Diagnosis of a Large Cohort of Egyptian Patients with Disorders of Sex Development","volume":"185","author":"Mazen","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s13023-021-01908-z","article-title":"Characteristics and Possible Mechanisms of 46, XY Differences in Sex Development Caused by Novel Compound Variants in NR5A1 and MAP3K1","volume":"16","author":"Cheng","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"900574","DOI":"10.3389\/fgene.2022.900574","article-title":"Novel Genomic Variants, Atypical Phenotypes and Evidence of a Digenic\/Oligogenic Contribution to Disorders\/Differences of Sex Development in a Large North African Cohort","volume":"13","author":"Zidoune","year":"2022","journal-title":"Front. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000445983","article-title":"Identification of NR5A1 Mutations and Possible Digenic Inheritance in 46,XY Gonadal Dysgenesis","volume":"10","author":"Mazen","year":"2016","journal-title":"Sex. Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/s41431-018-0202-7","article-title":"Broad Phenotypes in Heterozygous NR5A1 46,XY Patients with a Disorder of Sex Development: An Oligogenic Origin?","volume":"26","author":"Camats","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00439-018-1879-y","article-title":"Next-Generation Sequencing Reveals Genetic Landscape in 46, XY Disorders of Sexual Development Patients with Variable Phenotypes","volume":"137","author":"Wang","year":"2018","journal-title":"Hum. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez de LaPiscina, I., Mahmoud, R.A., Sauter, K.-S., Esteva, I., Alonso, M., Costa, I., Rial-Rodriguez, J.M., Rodr\u00edguez-Est\u00e9vez, A., Vela, A., and Castano, L. (2020). Variants of STAR, AMH and ZFPM2\/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228554"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.tig.2022.04.009","article-title":"Machine Learning Approaches to Explore Digenic Inheritance","volume":"38","author":"Okazaki","year":"2022","journal-title":"Trends Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmedgenet-2013-101713","article-title":"Digenic Inheritance in Medical Genetics","volume":"50","year":"2013","journal-title":"J. Med. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ajhg.2010.09.009","article-title":"Human Male Infertility Associated with Mutations in NR5A1 Encoding Steroidogenic Factor 1","volume":"87","author":"Bashamboo","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_71","first-page":"1505","article-title":"AR Suppresses Transcription of the LHbeta Subunit by Interacting with Steroidogenic Factor-1","volume":"15","author":"Jorgensen","year":"2001","journal-title":"Mol. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.diff.2022.04.002","article-title":"Mouse-Human Species Differences in Early Testicular Development and Its Implications","volume":"129","author":"Cunha","year":"2023","journal-title":"Differentiation"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"O\u2019Shaughnessy, P.J., Mitchell, R.T., Monteiro, A., O\u2019Hara, L., Cruickshanks, L., der Grinten, H.C., Brown, P., Abel, M., and Smith, L.B. (2019). Androgen Receptor Expression Is Required to Ensure Development of Adult Leydig Cells and to Prevent Development of Steroidogenic Cells with Adrenal Characteristics in the Mouse Testis. BMC Dev. Biol., 19.","DOI":"10.1186\/s12861-019-0189-5"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1210\/jc.2013-1278","article-title":"Identification of a Novel Androgen Receptor Mutation in a Family with Multiple Components Compatible with the Testicular Dysgenesis Syndrome","volume":"98","author":"Lottrup","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Lanciotti, L., Cofini, M., Leonardi, A., Bertozzi, M., Penta, L., and Esposito, S. (2019). Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS). Int. J. Environ. Res. Public. Health, 16.","DOI":"10.3390\/ijerph16071268"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1056\/NEJMc1010311","article-title":"A SOX9 Duplication and Familial 46,XX Developmental Testicular Disorder","volume":"364","author":"Cox","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1136\/jmedgenet-2014-102864","article-title":"Copy Number Variation of Two Separate Regulatory Regions Upstream of SOX9 Causes Isolated 46,XY or 46,XX Disorder of Sex Development","volume":"52","author":"Kim","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_78","first-page":"242","article-title":"Can Non-Coding NR5A1 Gene Variants Explain Phenotypes of Disorders of Sex Development?","volume":"16","author":"Werner","year":"2022","journal-title":"Sex. Dev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1210\/en.2011-1407","article-title":"Identification of an Enhancer in the Ad4BP\/SF-1 Gene Specific for Fetal Leydig Cells","volume":"153","author":"Shima","year":"2012","journal-title":"Endocrinology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.tem.2004.02.002","article-title":"Sex Determination: A \u201cwindow\u201d of DAX1 Activity","volume":"15","author":"Ludbrook","year":"2004","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1210\/me.2003-0159","article-title":"DAX-1, an Unusual Orphan Receptor at the Crossroads of Steroidogenic Function and Sexual Differentiation","volume":"17","author":"Lalli","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1210\/en.2011-1428","article-title":"Excess DAX1 Leads to XY Ovotesticular Disorder of Sex Development (DSD) in Mice by Inhibiting Steroidogenic Factor-1 (SF1) Activation of the Testis Enhancer of SRY-Box-9 (Sox9)","volume":"153","author":"Ludbrook","year":"2012","journal-title":"Endocrinology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1210\/jc.2007-0505","article-title":"Isolated 46,XY Gonadal Dysgenesis in Two Sisters Caused by a Xp21.2 Interstitial Duplication Containing the DAX1 Gene","volume":"92","author":"Barbaro","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1399-0004.2008.00980.x","article-title":"Gene Dosage Imbalances in Patients with 46,XY Gonadal DSD Detected by an in-House-Designed Synthetic Probe Set for Multiplex Ligation-Dependent Probe Amplification Analysis","volume":"73","author":"Barbaro","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"504904","DOI":"10.1155\/2012\/504904","article-title":"Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis","volume":"2012","author":"Barbaro","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/ng0894-497","article-title":"A Dosage Sensitive Locus at Chromosome Xp21 Is Involved in Male to Female Sex Reversal","volume":"7","author":"Bardoni","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Dong, Y., Yi, Y., Yao, H., Yang, Z., Hu, H., Liu, J., Gao, C., Zhang, M., Zhou, L., and Yi, X. (2016). Targeted Next-Generation Sequencing Identification of Mutations in Patients with Disorders of Sex Development. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0286-2"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00439-002-0791-6","article-title":"Gene Dosage of the Spermidine\/Spermine N(1)-Acetyltransferase (SSAT) Gene with Putrescine Accumulation in a Patient with a Xp21.1p22.12 Duplication and Keratosis Follicularis Spinulosa Decalvans (KFSD)","volume":"111","author":"Gimelli","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1093\/humrep\/deq167","article-title":"Array-CGH Analysis in Patients with Syndromic and Non-Syndromic XY Gonadal Dysgenesis: Evaluation of Array CGH as Diagnostic Tool and Search for New Candidate Loci","volume":"25","author":"Ledig","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4274\/jcrpe.galenos.2022.2022-3-15","article-title":"Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated to 46,XY Gonadal Dysgenesis","volume":"15","author":"Rjiba","year":"2023","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1515\/jpem-2012-0354","article-title":"Duplication of Dosage Sensitive Sex Reversal Area in a 46, XY Patient with Normal Sex Determining Region of Y Causing Complete Sex Reversal","volume":"26","author":"Sukumaran","year":"2013","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"White, S., Ohnesorg, T., Notini, A., Roeszler, K., Hewitt, J., Daggag, H., Smith, C., Turbitt, E., Gustin, S., and van den Bergen, J. (2011). Copy Number Variation in Patients with Disorders of Sex Development Due to 46,XY Gonadal Dysgenesis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017793"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zheng, G.Y., Chu, G.M., Li, P.P., and He, R. (2023). Phenotype and Genetic Characteristics in 20 Chinese Patients with 46,XY Disorders of Sex Development. J. Endocrinol. Investig., online ahead of print.","DOI":"10.1007\/s40618-023-02020-8"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/BF00352360","article-title":"A Family of Rapidly Evolving Genes from the Sex Reversal Critical Region in Xp21","volume":"6","author":"Dabovic","year":"1995","journal-title":"Mamm. Genome"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00439-007-0373-8","article-title":"Male-to-Female Sex Reversal Associated with an Approximately 250 Kb Deletion Upstream of NR0B1 (DAX1)","volume":"122","author":"Smyk","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Meinel, J.A., Yumiceba, V., K\u00fcnstner, A., Schultz, K., Kruse, N., Kaiser, F.J., Holterhus, P.-M., Claviez, A., Hiort, O., and Busch, H. (2022). Disruption of the Topologically Associated Domain at Xp21.2 Is Related to 46,XY Gonadal Dysgenesis. J. Med. Genet., online ahead of print.","DOI":"10.1136\/jmg-2022-108635"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Francese-Santos, A.P., Meinel, J.A., Piveta, C.S.C., Andrade, J.G.R., Barros, B.A., Fabbri-Scallet, H., Gil-da-Silva-Lopes, V.L., Guerra-Junior, G., K\u00fcnstner, A., and Busch, H. (2022). A Novel Look at Dosage-Sensitive Sex Locus Xp21.2 in a Case of 46,XY Partial Gonadal Dysgenesis without NR0B1 Duplication. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010494"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Miclea, D., Alkhzouz, C., Bucerzan, S., Grigorescu-Sido, P., Popp, R.A., Pascanu, I.M., Cret, V., Ghervan, C., Blaga, L., and Zaharie, G. (2021). Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development. Diagnostics, 11.","DOI":"10.3390\/diagnostics11112107"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1007\/s11033-019-04688-9","article-title":"Novel Frameshift Mutation of the NR0B1(DAX1) in Two Tall Adult Brothers","volume":"46","author":"Bertalan","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.3892\/mmr.2016.5006","article-title":"X-Linked Adrenal Hypoplasia Congenita and Hypogonadotropic Hypogonadism: Identification and in Vitro Study of a Novel Small Indel in the NR0B1 Gene","volume":"13","author":"Yu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/andr.12897","article-title":"De Novo Mutations in Idiopathic Male Infertility-A Pilot Study","volume":"9","author":"Maver","year":"2021","journal-title":"Andrology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"K45","DOI":"10.1530\/EJE-12-1055","article-title":"A Man with a DAX1\/NR0B1 Mutation, Normal Puberty, and an Intact Hypothalamic-Pituitary-Gonadal Axis but Deteriorating Oligospermia during Long-Term Follow-Up","volume":"168","author":"Oudet","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_103","first-page":"4501","article-title":"X-Linked Adrenal Hypoplasia Congenita: A Mutation in DAX1 Expands the Phenotypic Spectrum in Males and Females","volume":"84","author":"Seminara","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Mou, L., Xie, N., Yang, L., Liu, Y., Diao, R., Cai, Z., Li, H., and Gui, Y. (2015). A Novel Mutation of DAX-1 Associated with Secretory Azoospermia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133997"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/3822","article-title":"Role of Ahch in Gonadal Development and Gametogenesis","volume":"20","author":"Yu","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/ng1141","article-title":"Dax1 Is Required for Testis Determination","volume":"34","author":"Meeks","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1242\/dev.01890","article-title":"Gonadal Sex Reversal in Mutant Dax1 XY Mice: A Failure to Upregulate Sox9 in Pre-Sertoli Cells","volume":"132","author":"Bouma","year":"2005","journal-title":"Development"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s43032-021-00554-x","article-title":"Leydig Cell-Specific DAX1-Deleted Mice Has Higher Testosterone Level in the Testis During Pubertal Development","volume":"29","author":"Kumar","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000448726","article-title":"NR0B1 Frameshift Mutation in a Boy with Idiopathic Central Precocious Puberty","volume":"10","author":"Shima","year":"2016","journal-title":"Sex. Dev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000492496","article-title":"Next-Generation Sequencing Identifies Different Genetic Defects in 2 Patients with Primary Adrenal Insufficiency and Gonadotropin-Independent Precocious Puberty","volume":"90","author":"Guzzetti","year":"2018","journal-title":"Horm. Res. Paediatr."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1515\/jpem-2012-0086","article-title":"A Novel DAX-1 Mutation Presented with Precocious Puberty and Hypogonadotropic Hypogonadism in Different Members of a Large Pedigree","volume":"26","author":"Durmaz","year":"2013","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"90","DOI":"10.6065\/apem.2013.18.2.90","article-title":"Central Precocious Puberty in a Patient with X-Linked Adrenal Hypoplasia Congenita and Xp21 Contiguous Gene Deletion Syndrome","volume":"18","author":"Koh","year":"2013","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"104192","DOI":"10.1016\/j.ejmg.2021.104192","article-title":"A Novel Stop-Loss DAX1 Variant Affecting Its Protein-Interaction with SF1 Precedes the Adrenal Hypoplasia Congenital with Rare Spontaneous Precocious Puberty and Elevated Hypothalamic-Pituitary-Gonadal\/Adrenal Axis Responses","volume":"64","author":"Yang","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Polvani, S., Pepe, S., Milani, S., and Galli, A. (2019). COUP-TFII in Health and Disease. Cells, 9.","DOI":"10.3390\/cells9010101"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.mce.2016.10.010","article-title":"Leydig Cell Stem Cells: Identification, Proliferation and Differentiation","volume":"445","author":"Chen","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"van den Driesche, S., Walker, M., McKinnell, C., Scott, H.M., Eddie, S.L., Mitchell, R.T., Seckl, J.R., Drake, A.J., Smith, L.B., and Anderson, R.A. (2012). Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037064"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1111\/andr.12817","article-title":"A Comparative Analysis of Human Adult Testicular Cells Expressing Stem Leydig Cell Markers in the Interstitium, Vasculature, and Peritubular Layer","volume":"8","author":"Eliveld","year":"2020","journal-title":"Andrology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/andr.12150","article-title":"MEF2 and NR2F2 Cooperate to Regulate Akr1c14 Gene Expression in Mouse MA-10 Leydig Cells","volume":"4","author":"Brousseau","year":"2016","journal-title":"Andrology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1210\/js.2019-00266","article-title":"The Nuclear Receptor COUP-TFII Regulates Amhr2 Gene Transcription via a GC-Rich Promoter Element in Mouse Leydig Cells","volume":"3","author":"Mehanovic","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1530\/JME-13-0290","article-title":"The INSL3 Gene Is a Direct Target for the Orphan Nuclear Receptor, COUP-TFII, in Leydig Cells","volume":"53","author":"Giner","year":"2014","journal-title":"J. Mol. Endocrinol."},{"key":"ref_121","first-page":"26","article-title":"The Nuclear Receptor NR2F2 Activates Star Expression and Steroidogenesis in Mouse MA-10 and MLTC-1 Leydig Cells","volume":"91","author":"Robert","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"E1924","DOI":"10.1073\/pnas.1320735111","article-title":"Fetal Programming of Adult Leydig Cell Function by Androgenic Effects on Stem\/Progenitor Cells","volume":"111","author":"Kilcoyne","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Qin, J., Tsai, M.-J., and Tsai, S.Y. (2008). Essential Roles of COUP-TFII in Leydig Cell Differentiation and Male Fertility. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003285"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1086276","DOI":"10.3389\/fendo.2022.1086276","article-title":"Emerging Concepts on Leydig Cell Development in Fetal and Adult Testis","volume":"13","author":"Bhattacharya","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/humupd\/dmv008","article-title":"Morphological and Functional Maturation of Leydig Cells: From Rodent Models to Primates","volume":"21","author":"Teerds","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_126","first-page":"31","article-title":"The Nuclear Receptors SF1 and COUP-TFII Cooperate on the Insl3 Promoter in Leydig Cells","volume":"164","author":"Pierre","year":"2022","journal-title":"Reproduction"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Giner, X.C., Pierre, K.J., Robert, N.M., and Tremblay, J.J. (2022). A 35-Bp Conserved Region Is Crucial for Insl3 Promoter Activity in Mouse MA-10 Leydig Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315060"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"eabn9793","DOI":"10.1126\/sciadv.abn9793","article-title":"In Vitro Cellular Reprogramming to Model Gonad Development and Its Disorders","volume":"9","author":"Gonen","year":"2023","journal-title":"Sci. Adv."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/4\/691\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:18:54Z","timestamp":1760123934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/4\/691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":128,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["biom13040691"],"URL":"https:\/\/doi.org\/10.3390\/biom13040691","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]}}}