{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:09:33Z","timestamp":1791497373579,"version":"4.3.4"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Z01-ES102965, R00-HD096051"],"award-info":[{"award-number":["Z01-ES102965, R00-HD096051"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>In the 1940s, Alfred Jost demonstrated the necessity of testicular secretions, particularly androgens, for male internal and external genitalia differentiation. Since then, our knowledge of androgen impacts on differentiation of the male internal (Wolffian duct) and external genitalia (penis) has been drastically expanded upon. Between these two morphologically and functionally distinct organs, divergent signals facilitate the establishment of tissue-specific identities. Conversely, conserved actions of androgen signaling are present in both tissues and are largely responsible for the growth and expansion of the organs. In this review we synthesize the existing knowledge of the cell type-specific, organ specific, and conserved signaling mechanisms of androgens. Mechanistic studies on androgen signaling in the Wolffian duct and male external genitalia have largely been conducted in mouse model organisms. Therefore, the majority of the review is focused on mouse model studies.<\/jats:p>","DOI":"10.3389\/fendo.2022.910964","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T10:21:52Z","timestamp":1656584512000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["One Tool for Many Jobs: Divergent and Conserved Actions of Androgen Signaling in Male Internal Reproductive Tract and External Genitalia"],"prefix":"10.3389","volume":"13","author":[{"given":"Ciro M.","family":"Amato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humphrey H-C.","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-142X.2011.00482.x","article-title":"Essential Functions of Androgen Signaling Emerged Through the Developmental Analysis of Vertebrate Sex Characteristics","volume":"13","author":"Ogino","year":"2011","journal-title":"Evol Dev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1469-185X.1948.tb00462.x","article-title":"*Recherches Sur La Differenciation Sexuelle De Lembryon De Lapin .1. Introduction Et Embryologie Genitale Normale","volume":"36","author":"Jost","year":"1947","journal-title":"Arch Anat Microsc Mo"},{"key":"B3","first-page":"379","article-title":"Problems of Fetal Endocrinology - the Gonadal and Hypophyseal Hormones","volume":"8","author":"Jost","year":"1953","journal-title":"Recent Prog Horm Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1201","article-title":"Androgen Insensitivity Syndrome: Cliniical Features and Molecular Defects","volume":"7","author":"Galani","year":"2008","journal-title":"Hormones"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.78.3.8126121","article-title":"Characterization of Mutant Androgen Receptors Causing Partial Androgen Insensitivity Syndrome","volume":"78","author":"De Bellis","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6300(200003\/04)12:2<151::AID-AJHB1>3.0.CO;2-F","article-title":"How Sexually Dimorphic are We? Review and Synthesis","volume":"12","author":"Blackless","year":"2000","journal-title":"Am J Hum Biol"},{"key":"B7","first-page":"3","article-title":"Androgen Receptor Structure, Function and Biology: From Bench to Bedside","volume":"37","author":"Davey","year":"2016","journal-title":"Clin Biochem Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.17.3491","article-title":"Failure of Normal Adult Leydig Cell Development in Androgen-Receptor-Deficient Mice","volume":"115","author":"O'Shaughnessy","year":"2002","journal-title":"J Cell Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000499274","article-title":"Disorders of Sexual Development: Current Status and Progress in the Diagnostic Approach","volume":"13","author":"Garcia-Acero","year":"2020","journal-title":"Curr Urol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1542\/peds.81.6.866","article-title":"Worldwide Experience in Newborn Screening for Classical Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency","volume":"81","author":"Pang","year":"1988","journal-title":"Pediatrics"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1530\/REP-17-0064","article-title":"Steroidogenesis in Leydig Cells: Effects of Aging and Environmental Factors","volume":"154","author":"Wang","year":"2017","journal-title":"Reproduction"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/endocr\/bqab066","article-title":"Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling","volume":"162","author":"Kothandapani","year":"2021","journal-title":"Endocrinology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10787","article-title":"Identification and Selective Inhibition of an Isozyme of Steroid 5a-Reductase in Human Scalp","volume":"89","author":"Harris","year":"1992","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00002","article-title":"Non-Genomic Actions of the Androgen Receptor in Prostate Cancer","volume":"8","author":"Leung","year":"2017","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01884","article-title":"Genomic Actions of the Androgen Receptor are Required for Normal Male Sexual Differentiation in a Mouse Model","volume":"35","author":"Notini","year":"2005","journal-title":"J Mol Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"109557","DOI":"10.1016\/j.celrep.2021.109557","article-title":"Male Fertility in Mice Requires Classical and Nonclassical Androgen Signaling","volume":"36","author":"Cooke","year":"2021","journal-title":"Cell Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.diff.2021.08.002","article-title":"Cornification and Classical Versus Nonclassical Androgen Receptor Signaling in Mouse Penile\/Preputial Development","volume":"121","author":"Cunha","year":"2021","journal-title":"Differentiation"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioz079","article-title":"A Tale of Two Tracts: History, Current Advances, and Future Directions of Research on Sexual Differentiation of Reproductive Tracts","volume":"101","author":"Zhao","year":"2019","journal-title":"Biol Reprod"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.155540","article-title":"Understanding Normal and Abnormal Development of the Wolffian\/epididymal Duct by Using Transgenic Mice","volume":"17","author":"Murashima","year":"2015","journal-title":"Asian J Androl"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-1121","article-title":"Essential Roles of Androgen Signaling in Wolffian Duct Stabilization and Epididymal Cell Differentiation","volume":"152","author":"Murashima","year":"2011","journal-title":"Endocrinology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/endo-128-6-2867","article-title":"Androgen Receptor Expression in Developing Male Reproductive Organs","volume":"128","author":"Cooke","year":"1991","journal-title":"Endocrinology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai9136","article-title":"Elimination of the Male Reproductive Tract in the Female Embryo is Promoted by COUP-TFII in Mice","volume":"357","author":"Zhao","year":"2017","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0303-7207(01)00461-0","article-title":"Origin, Differentiation and Regulation of Fetal and Adult Leydig Cells","volume":"179","author":"Habert","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1242\/dev.106.2.235","article-title":"Induction of Functional Cytodifferentiation in the Epithelium of Tissue Recombinants. II. Instructive Induction of Wolffian Duct Epithelia by Neonatal Seminal Vesicle Mesenchyme","volume":"106","author":"Higgins","year":"1989","journal-title":"Development"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2008.00290.x","article-title":"Mesenchymal-Epithelial Interactions: Past, Present, and Future","volume":"76","author":"Cunha","year":"2008","journal-title":"Differentiation"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2005.0010","DOI":"10.1038\/msb4100014","article-title":"A Comprehensive Pathway Map of Epidermal Growth Factor Receptor Signaling","volume":"1","author":"Oda","year":"2005","journal-title":"Mol Syst Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.2.8593821","article-title":"Stimulation of Epidermal Growth Factor Gene Expression During the Fetal Mouse Reproductive Tract Differentiation: Role of Androgen and its Receptor","volume":"137","author":"Gupta","year":"1996","journal-title":"Endocrinology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.3.8603602","article-title":"The Role of Epidermal Growth Factor Receptor (EGFR) in Male Reproductive Tract Differentiation: Stimulation of EGFR Expression and Inhibition of Wolffian Duct Differentiation With Anti-EGFR Antibody","volume":"137","author":"Gupta","year":"1996","journal-title":"Endocrinology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2007.07.005","article-title":"Altered Trophoblast Proliferation is Insufficient to Account for Placental Dysfunction in Egfr Null Embryos","volume":"28","author":"Dackor","year":"2007","journal-title":"Placenta"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.12.2739","article-title":"Targeted Inactivation of the EGF and Amphiregulin Genes Reveals Distinct Roles for EGF Receptor Ligands in Mouse Mammary Gland Development","volume":"126","author":"Luetteke","year":"1999","journal-title":"Development"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01808","article-title":"COUP-TFII is Essential for Radial and Anteroposterior Patterning of the Stomach","volume":"132","author":"Takamoto","year":"2005","journal-title":"Development"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1242\/dev.076299","article-title":"COUP-TFII is Essential for Metanephric Mesenchyme Formation and Kidney Precursor Cell Survival","volume":"139","author":"Yu","year":"2012","journal-title":"Development"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702039104","article-title":"Deletion of the Orphan Nuclear Receptor COUP-TFII in Uterus Leads to Placental Deficiency","volume":"104","author":"Petit","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1159\/000513878","article-title":"Molecular Actions Underlying Wolffian Duct Regression in Sexual Differentiation of Murine Reproductive Tracts","volume":"14","author":"Zhao","year":"2020","journal-title":"Sex Dev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1903","article-title":"The Makings of Maleness: Towards an Integrated View of Male Sexual Development","volume":"7","author":"Wilhelm","year":"2006","journal-title":"Nat Rev Genet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.009324","article-title":"5' Hox Genes and Meis 1, a Hox-DNA Binding Cofactor, are Expressed in the Adult Mouse Epididymis","volume":"68","author":"Bomgardner","year":"2003","journal-title":"Biol Reprod"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(SICI)1097-0177(199901)214:1<1::AID-DVDY1>3.0.CO;2-2","article-title":"Hoxa-10 Deficient Male Mice Exhibit Abnormal Development of the Accessory Sex Organs","volume":"214","author":"Podlasek","year":"1999","journal-title":"Dev Dyn"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.5.1373","article-title":"Hoxa 11 Structure, Extensive Antisense Transcription, and Function in Male and Female Fertility","volume":"121","author":"Hsieh-Li","year":"1995","journal-title":"Development"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)68999-9","article-title":"Hoxa-13 Gene Mutation Results in Abnormal Seminal Vesicle and Prostate Development","volume":"161","author":"Podlasek","year":"1999","journal-title":"J Urol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.9.2687","article-title":"Mechanisms of Reduced Fertility in Hoxa-10 Mutant Mice: Uterine Homeosis and Loss of Maternal Hoxa-10 Expression","volume":"122","author":"Benson","year":"1996","journal-title":"Development"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/375791a0","article-title":"Absence of Radius and Ulna in Mice Lacking Hoxa-11 and Hoxd-11","volume":"375","author":"Davis","year":"1995","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.23.4781","article-title":"Gene Dosage-Dependent Effects of the Hoxa-13 and Hoxd-13 Mutations on Morphogenesis of the Terminal Parts of the Digestive and Urogenital Tracts","volume":"124","author":"Warot","year":"1997","journal-title":"Development"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22378","article-title":"Gene Expression in the Efferent Ducts, Epididymis, and Vas Deferens During Embryonic Development of the Mouse","volume":"239","author":"Snyder","year":"2010","journal-title":"Dev Dyn"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703445104","article-title":"Essential Roles of Inhibin Beta A in Mouse Epididymal Coiling","volume":"104","author":"Tomaszewski","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B45","doi-asserted-by":"publisher","first-page":"68","DOI":"10.4161\/org.4.2.5851","article-title":"Wnt Signal Transduction Pathways","volume":"4","author":"Komiya","year":"2008","journal-title":"Organogenesis"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1242\/dev.146589","article-title":"Wnt Signaling in Development and Tissue Homeostasis","volume":"145","author":"Steinhart","year":"2018","journal-title":"Development"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.02.025","article-title":"Epithelial Wnt\/betacatenin Signalling is Essential for Epididymal Coiling","volume":"412","author":"Kumar","year":"2016","journal-title":"Dev Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.11.016","article-title":"Beta-Catenin is Necessary to Keep Cells of Ureteric Bud\/Wolffian Duct Epithelium in a Precursor State","volume":"314","author":"Marose","year":"2008","journal-title":"Dev Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3363","article-title":"The Polycystin Complex Mediates Wnt\/Ca(2+) Signalling","volume":"18","author":"Kim","year":"2016","journal-title":"Nat Cell Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2013.07.006","article-title":"Pkd1 is Required for Male Reproductive Tract Development","volume":"130","author":"Nie","year":"2013","journal-title":"Mech Dev"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.11.043","article-title":"Defective Postnatal Development of the Male Reproductive Tract in LGR4 Knockout Mice","volume":"290","author":"Mendive","year":"2006","journal-title":"Dev Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.106.054619","article-title":"LGR4 Regulates the Postnatal Development and Integrity of Male Reproductive Tracts in Mice","volume":"76","author":"Hoshii","year":"2007","journal-title":"Biol Reprod"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0244","article-title":"The BMP Family Member Gdf7 is Required for Seminal Vesicle Growth, Branching Morphogenesis, and Cytodifferentiation","volume":"234","author":"Settle","year":"2001","journal-title":"Dev Biol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.01.023","article-title":"Region-Specific Regulation of Cell Proliferation by FGF Receptor Signaling During the Wolffian Duct Development","volume":"400","author":"Okazawa","year":"2015","journal-title":"Dev Biol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0012-1606(03)00250-1","article-title":"FGF-10 Plays an Essential Role in the Growth of the Fetal Prostate","volume":"261","author":"Donjacour","year":"2003","journal-title":"Dev Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.16.3693","article-title":"Prostatic Growth and Development are Regulated by FGF10","volume":"126","author":"Thomson","year":"1999","journal-title":"Development"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030210","article-title":"Pattern of Keratinocyte Growth Factor and Keratinocyte Growth Factor Receptor Expression During Mouse Fetal Development Suggests a Role in Mediating Morphogenetic Mesenchymal-Epithelial Interactions","volume":"203","author":"Finch","year":"1995","journal-title":"Dev Dyn"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.3.1074","article-title":"Keratinocyte Growth Factor Functions in Epithelial Induction During Seminal Vesicle Development","volume":"91","author":"Alarid","year":"1994","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.05.016","article-title":"Wnt9b Plays a Central Role in the Regulation of Mesenchymal to Epithelial Transitions Underlying Organogenesis of the Mammalian Urogenital System","volume":"9","author":"Carroll","year":"2005","journal-title":"Dev Cell"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1242\/dev.042226","article-title":"Vhnf1 Functions in Distinct Regulatory Circuits to Control Ureteric Bud Branching and Early Nephrogenesis","volume":"137","author":"Lokmane","year":"2010","journal-title":"Development"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1542\/peds.100.5.831","article-title":"Hypospadias Trends in Two US Surveillance Systems","volume":"100","author":"Paulozzi","year":"1997","journal-title":"Pediatrics"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-017-2864-5","article-title":"Hypospadias, All There is to Know","volume":"176","author":"van der Horst","year":"2017","journal-title":"Eur J Pediatr"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dms002","article-title":"Aetiology of Hypospadias: A Systematic Review of Genes and Environment","volume":"18","author":"van der Zanden","year":"2012","journal-title":"Hum Reprod Update"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e55587","DOI":"10.1371\/journal.pone.0055587","article-title":"Embryonic Origin and Remodeling of the Urinary and Digestive Outlets","volume":"8","author":"Wang","year":"2013","journal-title":"PloS One"},{"key":"B65","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1006\/dbio.2002.0668","article-title":"Sonic Hedgehog Signaling From the Urethral Epithelium Controls External Genital Development","volume":"247","author":"Perriton","year":"2002","journal-title":"Dev Biol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.diff.2019.08.003","article-title":"Temporal, Spatial, and Genetic Regulation of External Genitalia Development","volume":"110","author":"Haller","year":"2019","journal-title":"Differentiation"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1073\/pnas.2103856118","article-title":"Developmental and Sexual Dimorphic Atlas of the Prenatal Mouse External Genitalia at the Single-Cell Level","volume":"118","author":"Amato","year":"2021","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.160","article-title":"Genetic Analysis of the Role of Alx4 in the Coordination of Lower Body and External Genitalia Formation","volume":"22","author":"Matsumaru","year":"2014","journal-title":"Eur J Hum Genet"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.09.020","article-title":"Six1 and Eya1 are Critical Regulators of Peri-Cloacal Mesenchymal Progenitors During Genitourinary Tract Development","volume":"360","author":"Wang","year":"2011","journal-title":"Dev Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515981112","article-title":"Timing of Androgen Receptor Disruption and Estrogen Exposure Underlies a Spectrum of Congenital Penile Anomalies","volume":"112","author":"Zheng","year":"2015","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2010.03.079","article-title":"Morphology of Mouse External Genitalia: Implications for a Role of Estrogen in Sexual Dimorphism of the Mouse Genital Tubercle","volume":"184","author":"Yang","year":"2010","journal-title":"J Urol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117903","article-title":"An Illustrated Anatomical Ontology of the Developing Mouse Lower Urogenital Tract","volume":"142","author":"Georgas","year":"2015","journal-title":"Development"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.05.014","article-title":"Single Cell Transcriptomic Analysis of External Genitalia Reveals Complex and Sexually Dimorphic Cell Populations in the Early Genital Tubercle","volume":"477","author":"Armfield","year":"2021","journal-title":"Dev Biol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1210\/me.2008-0478","article-title":"Genetic Interactions of the Androgen and Wnt\/beta-Catenin Pathways for the Masculinization of External Genitalia","volume":"23","author":"Miyagawa","year":"2009","journal-title":"Mol Endocrinol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413273111","article-title":"Sexually Dimorphic Expression of Mafb Regulates Masculinization of the Embryonic Urethral Formation","volume":"111","author":"Suzuki","year":"2014","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1610471113","article-title":"Spatiotemporal Dynamics of Androgen Signaling Underlie Sexual Differentiation and Congenital Malformations of the Urethra and Vagina","volume":"113","author":"Larkins","year":"2016","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12241","article-title":"5\u03b1-Dihydrotestosterone Negatively Regulates Cell Proliferation of the Periurethral Ventral Mesenchyme During Urethral Tube Formation in the Murine Male Genital Tubercle","volume":"5","author":"Suzuki","year":"2017","journal-title":"Andrology"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609360200","article-title":"Essential Role for Co-Chaperone Fkbp52 But Not Fkbp51 in Androgen Receptor-Mediated Signaling and Physiology","volume":"282","author":"Yong","year":"2007","journal-title":"J Biol Chem"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1073\/pnas.2024067118","article-title":"Sexual Fate of Murine External Genitalia Development: Conserved Transcriptional Competency for Male-Biased Genes in Both Sexes","volume":"118","author":"Kajioka","year":"2021","journal-title":"Proc Natl Acad Sci U.S.A. 118"},{"key":"B80","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s42003-019-0336-3","article-title":"Mesenchymal Actomyosin Contractility is Required for Androgen-Driven Urethral Masculinization in Mice","volume":"2","author":"Acebedo","year":"2019","journal-title":"Commun Biol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1159\/000477452","article-title":"Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis","volume":"11","author":"Liu","year":"2017","journal-title":"Sex Dev"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.05.495","article-title":"Comparative Gene Expression Analysis of Genital Tubercle Development Reveals a Putative Appendicular Wnt7 Network for the Epidermal Differentiation","volume":"344","author":"Chiu","year":"2010","journal-title":"Dev Biol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1242\/dev.020586","article-title":"Tissue-Specific Requirements of Beta-Catenin in External Genitalia Development","volume":"135","author":"Lin","year":"2008","journal-title":"Development"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1111\/cga.12438","article-title":"Stage-Dependent Function of Wnt5a During Male External Genitalia Development","volume":"61","author":"Alcantara","year":"2021","journal-title":"Congenit Anom (Kyoto)"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa035","article-title":"Prenatal Low-Dose Methyltestosterone, But Not Dihydrotestosterone, Treatment Induces Penile Formation in Female Mice and Guinea Pigsdagger","volume":"102","author":"Wang","year":"2020","journal-title":"Biol Reprod"},{"key":"B86","first-page":"vi, 218","volume-title":"An Atlas for Staging Mammalian and Chick Embryos","author":"Butler","year":"1987"},{"key":"B87","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.diff.2018.08.001","article-title":"Development of the Human Penis and Clitoris","volume":"103","author":"Baskin","year":"2018","journal-title":"Differentiation"},{"key":"B88","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.tem.2010.10.002","article-title":"Estrogen and Androgen Receptors: Regulators of Fuel Homeostasis and Emerging Targets for Diabetes and Obesity","volume":"22","author":"Mauvais-Jarvis","year":"2011","journal-title":"Trends Endocrinol Metab"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/S0013-9351(03)00085-9","article-title":"Induction of Hypospadias in a Murine Model by Maternal Exposure to Synthetic Estrogens","volume":"94","author":"Suk Kim","year":"2004","journal-title":"Environ Res"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802586RR","article-title":"A Critical Role for Estrogen Signaling in Penis Development","volume":"33","author":"Govers","year":"2019","journal-title":"FASEB J"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy087","article-title":"Organizational Effects of the Antiandrogen, Vinclozolin, on Penis Development in the Mouse","volume":"99","author":"Amato","year":"2018","journal-title":"Biol Reprod"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-004-0419-9","article-title":"Regulation of External Genitalia Development by Concerted Actions of FGF Ligands and FGF Receptors","volume":"208","author":"Satoh","year":"2004","journal-title":"Anat Embryol (Berl)"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01778","article-title":"Development of the Mammalian Urethra is Controlled by Fgfr2-IIIb","volume":"132","author":"Petiot","year":"2005","journal-title":"Development"},{"key":"B94","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.mce.2014.11.002","article-title":"Estrogen Mediated Epithelial Proliferation in the Uterus is Directed by Stromal Fgf10 and Bmp8a","volume":"400","author":"Chung","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1413","article-title":"Estrogen Receptor-Alpha Signaling in Growth of the Ventral Prostate: Comparison of Neonatal Growth and Postcastration Regrowth","volume":"149","author":"Omoto","year":"2008","journal-title":"Endocrinology"},{"key":"B96","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.diff.2019.10.002","article-title":"Development of the Human Prepuce and its Innervation","volume":"111","author":"Cunha","year":"2020","journal-title":"Differentiation"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2015.57","article-title":"Current Understanding of Hypospadias: Relevance of Animal Models","volume":"12","author":"Cunha","year":"2015","journal-title":"Nat Rev Urol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.091504","article-title":"New Insights on the Morphology of Adult Mouse Penis","volume":"85","author":"Rodriguez","year":"2011","journal-title":"Biol Reprod"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1159\/000431010","article-title":"A Comprehensive Atlas of the Adult Mouse Penis","volume":"9","author":"Phillips","year":"2015","journal-title":"Sex Dev"},{"key":"B100","article-title":"A Histological Study of the Development of the Penis of Wild-Type and Androgen Insensitive Mice","volume":"153","author":"Murakami","year":"1987","journal-title":"J Anat."},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22708","article-title":"Analysis of the Effect of Estrogen\/Androgen Perturbation on Penile Development in Transgenic and Diethylstilbestrol-Treated Mice","volume":"296","author":"Blaschko","year":"2013","journal-title":"Anat Rec (Hoboken)"},{"key":"B102","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.diff.2019.08.005","article-title":"Androgen and Estrogen Receptor Expression in the Developing Human Penis and Clitoris","volume":"111","author":"Baskin","year":"2020","journal-title":"Differentiation"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/78161","article-title":"Insertion of Inhbb Into the Inhba Locus Rescues the Inhba-Null Phenotype and Reveals New Active Functions","volume":"25","author":"Brown","year":"2000","journal-title":"Nature"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34241","article-title":"Identification in Rats of a Programming Window for Reproductive Tract Masculinization, Disruption of Which Leads to Hypospadias and Cryptorchidism","volume":"118","author":"Welsh","year":"2008","journal-title":"J Clin Invest"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1139\/y95-718","article-title":"Effects of Short-Term Exposure to Hydroxyflutamide in utero Dev Reprod Tract Male Mice","volume":"73","author":"Silversides","year":"1995","journal-title":"Can J Physiol Pharmacol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0028","article-title":"The Critical Time Window for Androgen-Dependent Development of the Wolffian Duct in the Rat","volume":"148","author":"Welsh","year":"2007","journal-title":"Endocrinology"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2011.01236.x","article-title":"The Effect of Dihydrotestosterone Exposure During or Prior to the Masculinization Programming Window on Reproductive Development in Male and Female Rats","volume":"35","author":"Dean","year":"2012","journal-title":"Int J Androl"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.09.041","article-title":"Pattern Formation of an Epithelial Tubule by Mechanical Instability During Epididymal Development","volume":"9","author":"Hirashima","year":"2014","journal-title":"Cell Rep"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24277","article-title":"Tissue-Specific Roles of FGF Signaling in External Genitalia Development","volume":"244","author":"Harada","year":"2015","journal-title":"Dev Dyn"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.910964\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T10:21:58Z","timestamp":1656584518000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.910964\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":109,"alternative-id":["10.3389\/fendo.2022.910964"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.910964","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]},"article-number":"910964"}}