This volume presents state-of-the-art research from the various disciplines that define the leading edges of bladder research. The most current developments are presented, as well as an analysis of research, new tactics for unresolved problems, critical evaluations of the most current theories, together with the development of new theories and approaches as needed. The volume is divided into five sections: epithelial-mesenchymal interactions in the bladder; muscle and extracellular matrix in the bladder; nerves and pharmacology in the bladder; infection, immunology, and interstitial cystitis in the bladder; and cancer of the bladder.

This book focuses on the current basic science research of hypospadias and genital development. Congenital anomalies of the genitalia are the second most common birth abnormality besides congenital heart defects. Genital anomalies come in many varieties with the most common abnormality being hypospadias. The etiology of hypospadias remains unknown and the incidence is doubling in western countries with no definable explanation. It therefore seems especially germane to study this common congenital anomaly with a baseline incidence of 1/125-250 newborn males.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D.ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII.ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex­ tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol­ ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ­ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis­ tant. I hope you find this resource useful. Laurence S. Baskin, M.D.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex­ tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol­ ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ­ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis­ tant. I hope you find this resource useful. Laurence S. Baskin, M.D.

This volume presents state-of-the-art research from the various disciplines that define the leading edges of bladder research. The most current developments are presented, as well as an analysis of research, new tactics for unresolved problems, critical evaluations of the most current theories, together with the development of new theories and approaches as needed. The volume is divided into five sections: epithelial-mesenchymal interactions in the bladder; muscle and extracellular matrix in the bladder; nerves and pharmacology in the bladder; infection, immunology, and interstitial cystitis in the bladder; and cancer of the bladder.

This book focuses on the current basic science research of hypospadias and genital development. Congenital anomalies of the genitalia are the second most common birth abnormality besides congenital heart defects. Genital anomalies come in many varieties with the most common abnormality being hypospadias. The etiology of hypospadias remains unknown and the incidence is doubling in western countries with no definable explanation. It therefore seems especially germane to study this common congenital anomaly with a baseline incidence of 1/125-250 newborn males.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D.ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII.ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex­ tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol­ ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ­ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis­ tant. I hope you find this resource useful. Laurence S. Baskin, M.D.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex­ tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol­ ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ­ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis­ tant. I hope you find this resource useful. Laurence S. Baskin, M.D.