{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:48:33Z","timestamp":1790434113912,"version":"4.1.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T00:00:00Z","timestamp":1428364800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Urol"],"published-print":{"date-parts":[[2015,5]]},"DOI":"10.1038\/nrurol.2015.57","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T09:31:40Z","timestamp":1428485500000},"page":"271-280","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Current understanding of hypospadias: relevance of animal models"],"prefix":"10.1038","volume":"12","author":[{"given":"Gerald R.","family":"Cunha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriane","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Risbridger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hutson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence S.","family":"Baskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,4,7]]},"reference":[{"key":"BFnrurol201557_CR1","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/S0022-5347(05)67861-5","volume":"163","author":"LS Baskin","year":"2000","unstructured":"Baskin, L. S. Hypospadias and urethral development. J. Urol. 163, 951\u2013956 (2000).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR2","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1542\/peds.100.5.831","volume":"100","author":"LJ Paulozzi","year":"1997","unstructured":"Paulozzi, L. J., Erickson, J. D. & Jackson, R. J. Hypospadias trends in two US surveillance systems. Pediatrics 100, 831\u2013834 (1997).","journal-title":"Pediatrics"},{"key":"BFnrurol201557_CR3","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.juro.2013.01.091","volume":"190","author":"OT Lee","year":"2013","unstructured":"Lee, O. T., Durbin-Johnson, B. & Kurzrock, E. A. Predictors of secondary surgery after hypospadias repair: a population based analysis of 5,000 patients. J. Urol. 190, 251\u2013255 (2013).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.mce.2011.01.006","volume":"335","author":"N Kalfa","year":"2011","unstructured":"Kalfa, N., Philibert, P., Baskin, L. S. & Sultan, C. Hypospadias: interactions between environment and genetics. Mol. Cell. Endocrinol. 335, 89\u201395 (2011).","journal-title":"Mol. Cell. Endocrinol."},{"key":"BFnrurol201557_CR5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.juro.2010.03.051","volume":"184","author":"JH Yiee","year":"2010","unstructured":"Yiee, J. H. & Baskin, L. S. Environmental factors in genitourinary development. J. Urol. 184, 34\u201341 (2010).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR6","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/ncpuro0783","volume":"4","author":"E Willingham","year":"2007","unstructured":"Willingham, E. & Baskin, L. S. Candidate genes and their response to environmental agents in the etiology of hypospadias. Nat. Clin. Pract. Urol. 4, 270\u2013279 (2007).","journal-title":"Nat. Clin. Pract. Urol."},{"key":"BFnrurol201557_CR7","doi-asserted-by":"publisher","first-page":"e39","DOI":"10.1016\/j.fertnstert.2007.12.024","volume":"89","author":"LS Baskin","year":"2008","unstructured":"Baskin, L. S. Can we prevent hypospadias? Fertil. Steril. 89, e39 (2008).","journal-title":"Fertil. Steril."},{"key":"BFnrurol201557_CR8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1476-069X-5-4","volume":"5","author":"J Buckley","year":"2006","unstructured":"Buckley, J., Willingham, E., Agras, K. & Baskin, L. S. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice. Environ. Health 5, 4 (2006).","journal-title":"Environ. Health"},{"key":"BFnrurol201557_CR9","first-page":"491","volume":"31","author":"J Imperato-McGinley","year":"1984","unstructured":"Imperato-McGinley, J. 5\u03b1 Reductase deficiency in man. Prog. Cancer Res. Therap. 31, 491\u2013496 (1984).","journal-title":"Prog. Cancer Res. Therap."},{"key":"BFnrurol201557_CR10","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0013-9351(03)00085-9","volume":"94","author":"KS Kim","year":"2004","unstructured":"Kim, K. S.  et al. Induction of hypospadias in a murine model by maternal exposure to synthetic estrogens. Environ. Res. 94, 267\u2013275 (2004).","journal-title":"Environ. Res."},{"key":"BFnrurol201557_CR11","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/S0022-5347(05)65358-X","volume":"167","author":"Y Kojima","year":"2002","unstructured":"Kojima, Y.  et al. Spermatogenesis, fertility and sexual behavior in a hypospadiac mouse model. J. Urol. 167, 1532\u20131537 (2002).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR12","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.juro.2006.03.078","volume":"176","author":"E Willingham","year":"2006","unstructured":"Willingham, E.  et al. Steroid receptors and mammalian penile development: an unexpected role for progesterone receptor? J. Urol. 176, 728\u2013733 (2006).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR13","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S0022-5347(05)00188-6","volume":"175","author":"E Willingham","year":"2006","unstructured":"Willingham, E., Agras, K., Vilela, M. & Baskin, L. S. Loratadine exerts estrogen-like effects and disrupts penile development in the mouse. J. Urol. 175, 723\u2013726 (2006).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR14","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1001\/archpedi.159.10.957","volume":"159","author":"SL Carmichael","year":"2005","unstructured":"Carmichael, S. L.  et al. Maternal progestin intake and risk of hypospadias. Arch. Pediatr. Adolesc. Med. 159, 957\u2013962 (2005).","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"BFnrurol201557_CR15","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1289\/ehp.11933","volume":"117","author":"G Ormond","year":"2009","unstructured":"Ormond, G.  et al. Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ. Health Perspect. 117, 303\u2013307 (2009).","journal-title":"Environ. Health Perspect."},{"key":"BFnrurol201557_CR16","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1289\/ehp.8100","volume":"113","author":"SH Swan","year":"2005","unstructured":"Swan, S. H.  et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ. Health Perspect. 113, 1056\u20131061 (2005).","journal-title":"Environ. Health Perspect."},{"key":"BFnrurol201557_CR17","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1177\/074823379901500108","volume":"15","author":"J Ostby","year":"1999","unstructured":"Ostby, J.  et al. The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicol. Ind. Health 15, 80\u201393 (1999).","journal-title":"Toxicol. Ind. Health"},{"key":"BFnrurol201557_CR18","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1177\/0192623308329478","volume":"37","author":"CV Rider","year":"2009","unstructured":"Rider, C. V.  et al. Cumulative effects of in utero administration of mixtures of \u201cantiandrogens\u201d on male rat reproductive development. Toxicologic Pathol. 37, 100\u2013113 (2009).","journal-title":"Toxicologic Pathol."},{"key":"BFnrurol201557_CR19","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/S0022-5347(01)62711-3","volume":"160","author":"LS Baskin","year":"1998","unstructured":"Baskin, L. S., Erol, A., Li, Y. W. & Cunha, G. R. Anatomical studies of hypospadias. J. Urol. 160, 1108\u20131115 (1998).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR20","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.jpedsurg.2005.11.059","volume":"41","author":"LS Baskin","year":"2006","unstructured":"Baskin, L. S. & Ebbers, M. B. Hypospadias: anatomy, etiology, and technique. J. Pediatr. Surg. 41, 463\u2013472 (2006).","journal-title":"J. Pediatr. Surg."},{"key":"BFnrurol201557_CR21","volume-title":"Gray's Anatomy","author":"CD Clemente","year":"1985","unstructured":"Clemente, C. D. (ed.) Gray's Anatomy (Lea & Febiger, 1985)."},{"key":"BFnrurol201557_CR22","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1095\/biolreprod.111.091504","volume":"85","author":"E Rodriguez Jr.","year":"2011","unstructured":"Rodriguez, E., Jr.  et al. New insights on the morphology of adult mouse penis. Biol. Reprod. 85, 1216\u20131221 (2011).","journal-title":"Biol. Reprod."},{"key":"BFnrurol201557_CR23","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1002\/ar.22708","volume":"296","author":"SD Blaschko","year":"2013","unstructured":"Blaschko, S. D.  et al. Analysis of the effect of estrogen\/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice. Anat. Rec. (Hoboken) 296, 1127\u20131141 (2013).","journal-title":"Anat. Rec. (Hoboken)"},{"key":"BFnrurol201557_CR24","first-page":"589","volume":"124","author":"WA Beresford","year":"1977","unstructured":"Beresford, W. A. & Burkart, S. The penile bone and anterior process of the rat in scanning electron microscopy. J. Anat. 124, 589\u2013597 (1977).","journal-title":"J. Anat."},{"key":"BFnrurol201557_CR25","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/(SICI)1097-4687(200002)243:2<187::AID-JMOR7>3.0.CO;2-4","volume":"243","author":"K Izumi","year":"2000","unstructured":"Izumi, K., Yamaoka, I. & Murakami, R. Ultrastructure of the developing fibrocartilage of the os penis of rat. J. Morphol. 243, 187\u2013191 (2000).","journal-title":"J. Morphol."},{"key":"BFnrurol201557_CR26","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.diff.2014.09.005","volume":"88","author":"P Mahawong","year":"2014","unstructured":"Mahawong, P.  et al. Prenatal diethylstilbestrol induces malformation of the external genitalia of male and female mice and persistent second-generation developmental abnormalities of the external genitalia in two mouse strains. Differentiation 88, 51\u201369 (2014).","journal-title":"Differentiation"},{"key":"BFnrurol201557_CR27","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.diff.2014.09.004","volume":"88","author":"P Mahawong","year":"2014","unstructured":"Mahawong, P.  et al. Comparative effects of neonatal diethylstilbestrol on external genitalia development in adult males of two mouse strains with differential estrogen sensitivity. Differentiation 88, 70\u201383 (2014).","journal-title":"Differentiation"},{"key":"BFnrurol201557_CR28","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1530\/REP-07-0207","volume":"134","author":"HO Goyal","year":"2007","unstructured":"Goyal, H. O., Braden, T. D., Williams, C. S. & Williams, J. W. Role of estrogen in induction of penile dysmorphogenesis: a review. Reproduction 134, 199\u2013208 (2007).","journal-title":"Reproduction"},{"key":"BFnrurol201557_CR29","volume-title":"The Developing Human","author":"KL Moore","year":"2003","unstructured":"Moore, K. L. & Persaud, T. V. N. The Developing Human (Saunders, 2003)."},{"key":"BFnrurol201557_CR30","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1046\/j.1432-0436.2003.7108001.x","volume":"71","author":"G Yamada","year":"2003","unstructured":"Yamada, G., Satoh, Y., Baskin, L. S. & Cunha, G. R. Cellular and molecular mechanisms of development of the external genitalia. Differentiation 71, 445\u2013460 (2003).","journal-title":"Differentiation"},{"key":"BFnrurol201557_CR31","doi-asserted-by":"publisher","unstructured":"Li, Y.  et al. Canalization of the urethral plate precedes fusion of the urethral folds during male penile urethral development: the double zipper hypothesis. J. Urology \n                    http:\/\/dx.doi.org\/10.1016\/j.juro.2014.09.108\n                    \n                  .","DOI":"10.1016\/j.juro.2014.09.108"},{"key":"BFnrurol201557_CR32","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.ydbio.2008.03.017","volume":"318","author":"AW Seifert","year":"2008","unstructured":"Seifert, A. W., Harfe, B. D. & Cohn, M. J. Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum. Dev. Biol. 318, 143\u201352 (2008).","journal-title":"Dev. Biol."},{"key":"BFnrurol201557_CR33","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.bjps.2003.08.018","volume":"57","author":"PJ Hynes","year":"2004","unstructured":"Hynes, P. J. & Fraher, J. P. The development of the male genitourinary system: II. The origin and formation of the urethral plate. Br. J. Plast. Surg. 57, 112\u2013121 (2004).","journal-title":"Br. J. Plast. Surg."},{"key":"BFnrurol201557_CR34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.bjps.2003.08.017","volume":"57","author":"PJ Hynes","year":"2004","unstructured":"Hynes, P. J. & Fraher, J. P. The development of the male genitourinary system: III. The formation of the spongiose and glandar urethra. Br. J. Plast. Surg. 57, 203\u201314 (2004).","journal-title":"Br. J. Plast. Surg."},{"key":"BFnrurol201557_CR35","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s004410000345","volume":"305","author":"LS Baskin","year":"2001","unstructured":"Baskin, L. S.  et al. Urethral seam formation and hypospadias. Cell Tissue Res. 305, 379\u2013387 (2001).","journal-title":"Cell Tissue Res."},{"key":"BFnrurol201557_CR36","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1111\/j.1464-410X.2003.04511.x","volume":"92","author":"S Yucel","year":"2003","unstructured":"Yucel, S., Cavalcanti, A. G., Desouza, A., Wang, Z. & Baskin, L. S. The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle. BJU Int. 92, 1016\u20131021 (2003).","journal-title":"BJU Int."},{"key":"BFnrurol201557_CR37","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1016\/j.juro.2013.02.3198","volume":"190","author":"BJ Schlomer","year":"2013","unstructured":"Schlomer, B. J.  et al. Sexual differentiation in the male and female mouse from days 0 to 21: a detailed and novel morphometric description. J. Urol. 190, 1610\u20131617 (2013).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR38","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.diff.2012.07.003","volume":"84","author":"E Rodriguez Jr","year":"2012","unstructured":"Rodriguez, E. Jr  et al. Specific morphogenetic events in mouse external genitalia sex differentiation are responsive\/dependent upon androgens and\/or estrogens. Differentiation 84, 269\u2013279 (2012).","journal-title":"Differentiation"},{"key":"BFnrurol201557_CR39","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1006\/dbio.2002.0668","volume":"247","author":"CL Perriton","year":"2002","unstructured":"Perriton, C. L., Powles, N., Chiang, C., Maconochie, M. K. & Cohn, M. J. Sonic hedgehog signaling from the urethral epithelium controls external genital development. Dev. Biol. 247, 26\u201346 (2002).","journal-title":"Dev. Biol."},{"key":"BFnrurol201557_CR40","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1242\/dev.01778","volume":"132","author":"A Petiot","year":"2005","unstructured":"Petiot, A., Perriton, C. L., Dickson, C. & Cohn, M. J. Development of the mammalian urethra is controlled by Fgfr2-IIIb. Development 132, 2441\u20132450 (2005).","journal-title":"Development"},{"key":"BFnrurol201557_CR41","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1053\/j.sempedsurg.2011.03.003","volume":"20","author":"D Kluth","year":"2011","unstructured":"Kluth, D., Fiegel, H. C., Geyer, C. & Metzger, R. Embryology of the distal urethra and external genitals. Semin. Pediatr. Surg. 20, 176\u2013187 (2011).","journal-title":"Semin. Pediatr. Surg."},{"key":"BFnrurol201557_CR42","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1210\/endo.142.6.8211","volume":"142","author":"X Li","year":"2001","unstructured":"Li, X.  et al. Altered structure and function of reproductive organs in transgenic male mice overexpressing human aromatase. Endocrinology 142, 2435\u20132442 (2001).","journal-title":"Endocrinology"},{"key":"BFnrurol201557_CR43","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1093\/toxsci\/kfi159","volume":"85","author":"PM Foster","year":"2005","unstructured":"Foster, P. M. & Harris, M. W. Changes in androgen-mediated reproductive development in male rat offspring following exposure to a single oral dose of flutamide at different gestational ages. Toxicol. Sci. 85, 1024\u20131032 (2005).","journal-title":"Toxicol. Sci."},{"key":"BFnrurol201557_CR44","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1093\/humupd\/7.3.248","volume":"7","author":"LE Gray","year":"2001","unstructured":"Gray, L. E.  et al. Effects of environmental antiandrogens on reproductive development in experimental animals. Hum. Reprod. Update 7, 248\u2013264 (2001).","journal-title":"Hum. Reprod. Update"},{"key":"BFnrurol201557_CR45","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/j.1365-2605.2008.00866.x","volume":"31","author":"S Christiansen","year":"2008","unstructured":"Christiansen, S.  et al. Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat. Int. J. Androl. 31, 241\u2013248 (2008).","journal-title":"Int. J. Androl."},{"key":"BFnrurol201557_CR46","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1289\/ehp.0900689","volume":"117","author":"S Christiansen","year":"2009","unstructured":"Christiansen, S.  et al. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ. Health Perspect. 117, 1839\u20131846 (2009).","journal-title":"Environ. Health Perspect."},{"key":"BFnrurol201557_CR47","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/toxsci\/kfg128","volume":"74","author":"CJ Bowman","year":"2003","unstructured":"Bowman, C. J., Barlow, N. J., Turner, K. J., Wallace, D. G. & Foster, P. M. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol. Sci. 74, 393\u2013406 (2003).","journal-title":"Toxicol. Sci."},{"key":"BFnrurol201557_CR48","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1006\/taap.1993.1041","volume":"119","author":"RL Clark","year":"1993","unstructured":"Clark, R. L.  et al. Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5 \u03b1-reductase inhibitor. Toxicol. Appl. Pharmacol. 119, 34\u201340 (1993).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"BFnrurol201557_CR49","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1093\/humrep\/deg273","volume":"18","author":"JS Fisher","year":"2003","unstructured":"Fisher, J. S., Macpherson, S., Marchetti, N. & Sharpe, R. M. Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate. Hum. Reprod. 18, 1383\u20131394 (2003).","journal-title":"Hum. Reprod."},{"key":"BFnrurol201557_CR50","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/j.1365-2605.2005.00563.x","volume":"29","author":"PM Foster","year":"2006","unstructured":"Foster, P. M. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int. J. Androl. 29, 140\u2013147 (2006).","journal-title":"Int. J. Androl."},{"key":"BFnrurol201557_CR51","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1530\/REP-12-0266","volume":"144","author":"GR Klinefelter","year":"2012","unstructured":"Klinefelter, G. R.  et al. Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol. Reproduction 144, 747\u2013761 (2012).","journal-title":"Reproduction"},{"key":"BFnrurol201557_CR52","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1677\/joe.0.1280395","volume":"128","author":"T Iguchi","year":"1991","unstructured":"Iguchi, T., Uesugi, Y., Takasugi, N. & Petrow, V. Quantitative analysis of the development of genital organs from the urogenital sinus of the fetal male mouse treated prenatally with a 5 \u03b1-reductase inhibitor. J. Endocrinol. 128, 395\u2013401 (1991).","journal-title":"J. Endocrinol."},{"key":"BFnrurol201557_CR53","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1139\/y95-718","volume":"73","author":"DW Silversides","year":"1995","unstructured":"Silversides, D. W., Price, C. A. & Cooke, G. M. Effects of short-term exposure to hydroxyflutamide in utero on the development of the reproductive tract in male mice. Can. J. Physiol. Pharmacol. 73, 1582\u20131588 (1995).","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"BFnrurol201557_CR54","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.ydbio.2004.03.027","volume":"271","author":"C Dravis","year":"2004","unstructured":"Dravis, C.  et al. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev. Biol. 271, 272\u2013290 (2004).","journal-title":"Dev. Biol."},{"key":"BFnrurol201557_CR55","doi-asserted-by":"publisher","first-page":"5026","DOI":"10.1074\/jbc.M609360200","volume":"282","author":"W Yong","year":"2007","unstructured":"Yong, W.  et al. Essential role for Co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology. J. Biol. Chem. 282, 5026\u20135036 (2007).","journal-title":"J. Biol. Chem."},{"key":"BFnrurol201557_CR56","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.jpurol.2007.01.199","volume":"3","author":"S Yucel","year":"2007","unstructured":"Yucel, S., Dravis, C., Garcia, N., Henkemeyer, M. & Baker, L. A. Hypospadias and anorectal malformations mediated by Eph\/ephrin signaling. J. Pediatr. Urol. 3, 354\u2013363 (2007).","journal-title":"J. Pediatr. Urol."},{"key":"BFnrurol201557_CR57","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.tox.2007.01.018","volume":"232","author":"J Jiang","year":"2007","unstructured":"Jiang, J., Ma, L., Yuan, L., Wang, X. & Zhang, W. Study on developmental abnormalities in hypospadiac male rats induced by maternal exposure to di-n-butyl phthalate (DBP). Toxicology 232, 286\u2013293 (2007).","journal-title":"Toxicology"},{"key":"BFnrurol201557_CR58","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1530\/rep.1.00227","volume":"128","author":"Y Sajjad","year":"2004","unstructured":"Sajjad, Y., Quenby, S., Nickson, P., Lewis-Jones, D. I. & Vince, G. Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos. Reproduction 128, 331\u2013339 (2004).","journal-title":"Reproduction"},{"key":"BFnrurol201557_CR59","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/S0022-5347(17)32757-X","volume":"152","author":"RI Silver","year":"1994","unstructured":"Silver, R. I.  et al. Expression and regulation of steroid 5 \u03b1-reductase 2 in prostate disease. J. Urol. 152, 433\u2013437 (1994).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR60","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/S0140-6736(02)08152-7","volume":"359","author":"H Klip","year":"2002","unstructured":"Klip, H.  et al. Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study. Lancet 359, 1102\u20131107 (2002).","journal-title":"Lancet"},{"key":"BFnrurol201557_CR61","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1210\/jc.2002-021085","volume":"88","author":"C Crescioli","year":"2003","unstructured":"Crescioli, C.  et al. Expression of functional estrogen receptors in human fetal male external genitalia. J. Clin. Endocrinol. Metab. 88, 1815\u20131824 (2003).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"BFnrurol201557_CR62","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1210\/jcem-59-4-665","volume":"59","author":"GD Berkovitz","year":"1984","unstructured":"Berkovitz, G. D., Fujimoto, M., Brown, T. R., Brodie, A. M. & Migeon, C. J. Aromatase activity in cultured human genital skin fibroblasts. J. Clin. Endocrinol. Metab. 59, 665\u2013671 (1984).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"BFnrurol201557_CR63","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1677\/jme.1.01548","volume":"33","author":"S Jesmin","year":"2004","unstructured":"Jesmin, S.  et al. Aromatase is abundantly expressed by neonatal rat penis but downregulated in adulthood. J. Mol. Endocrinol. 33, 343\u2013359 (2004).","journal-title":"J. Mol. Endocrinol."},{"key":"BFnrurol201557_CR64","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1095\/biolreprod.110.089508","volume":"85","author":"T Yonezawa","year":"2011","unstructured":"Yonezawa, T., Higashi, M., Yoshioka, K. & Mutoh, K. Distribution of aromatase and sex steroid receptors in the baculum during the rat life cycle: effects of estrogen during the early development of the baculum. Biol. Reprod. 85, 105\u2013112 (2011).","journal-title":"Biol. Reprod."},{"key":"BFnrurol201557_CR65","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/ng.721","volume":"43","author":"LF van der Zanden","year":"2011","unstructured":"van der Zanden, L. F.  et al. Common variants in DGKK are strongly associated with risk of hypospadias. Nat. Genet. 43, 48\u201350 (2011).","journal-title":"Nat. Genet."},{"key":"BFnrurol201557_CR66","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/ng.3063","volume":"46","author":"F Geller","year":"2014","unstructured":"Geller, F.  et al. Genome-wide association analyses identify variants in developmental genes associated with hypospadias. Nat. Genet. 46, 957\u2013963 (2014).","journal-title":"Nat. Genet."},{"key":"BFnrurol201557_CR67","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1016\/j.juro.2007.01.014","volume":"177","author":"Z Wang","year":"2007","unstructured":"Wang, Z.  et al. Up-regulation of estrogen responsive genes in hypospadias: microarray analysis. J. Urol. 177, 1939\u20131946 (2007).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR68","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1203\/01.pdr.0000187796.28007.2d","volume":"58","author":"B Liu","year":"2005","unstructured":"Liu, B.  et al. Activating transcription factor 3 is up-regulated in patients with hypospadias. Pediatr. Res. 58, 1280\u20131283 (2005).","journal-title":"Pediatr. Res."},{"key":"BFnrurol201557_CR69","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.juro.2010.12.066","volume":"185","author":"L Qiao","year":"2011","unstructured":"Qiao, L., Tasian, G. E., Zhang, H., Cunha, G. R. & Baskin, L. ZEB1 is estrogen responsive in vitro in human foreskin cells and is over expressed in penile skin in patients with severe hypospadias. J. Urol. 185, 1888\u20131893 (2011).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR70","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/j.juro.2008.07.066","volume":"180","author":"N Kalfa","year":"2008","unstructured":"Kalfa, N.  et al. Genomic variants of ATF3 in patients with hypospadias. J. Urol. 180, 2183\u20132188 (2008).","journal-title":"J. Urol."},{"key":"BFnrurol201557_CR71","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1093\/humupd\/dms002","volume":"18","author":"LF van der Zanden","year":"2012","unstructured":"van der Zanden, L. F.  et al. Aetiology of hypospadias: a systematic review of genes and environment. Hum. Reprod. Update 18, 260\u2013283 (2012).","journal-title":"Hum. Reprod. Update"}],"container-title":["Nature Reviews Urology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nrurol.2015.57.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrurol.2015.57","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrurol.2015.57.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T04:14:22Z","timestamp":1684469662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nrurol.2015.57"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,7]]},"references-count":71,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["BFnrurol201557"],"URL":"https:\/\/doi.org\/10.1038\/nrurol.2015.57","relation":{},"ISSN":["1759-4812","1759-4820"],"issn-type":[{"value":"1759-4812","type":"print"},{"value":"1759-4820","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,7]]},"assertion":[{"value":"7 April 2015","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2015","order":2,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":3,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the version of this article initially published online, the legend of Figure 5h contained a labelling error (f instead of h). The error has been corrected for the print, HTML and PDF versions of the article.","order":4,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}