The Genetic and Environmental Factors Underlying Hypospadias

被引：148

作者：

Bouty, Aurore ^{[1
,2
,3
]}

Ayers, Katie L. ^{[1
,3
]}

Pask, Andrew ^{[4
]}

Heloury, Yves ^{[1
,2
,3
]}

Sinclair, Andrew H. ^{[1
,3
]}

机构：

[1] Royal Childrens Hosp, Murdoch Childrens Res Inst, 50 Flemington Rd, Parkville, Vic 3052, Australia

[2] Royal Childrens Hosp, Dept Surg, Parkville, Vic 3052, Australia

[3] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia

[4] Univ Melbourne, Dept Zool, Melbourne, Vic, Australia

来源：

SEXUAL DEVELOPMENT | 2015年 / 9卷 / 05期

关键词：

Disorders of sexual development; Hypospadias; Penis; Phallus; Urethra; ANDROGEN RECEPTOR GENE; EXTERNAL GENITALIA DEVELOPMENT; ACTIVATING TRANSCRIPTION FACTOR-3; ENDOCRINE DISRUPTING CHEMICALS; SEVERE PENOSCROTAL HYPOSPADIAS; MESSENGER-RNA EXPRESSION; ADVERSE BIRTH OUTCOMES; BODY-MASS INDEX; ADRENAL INSUFFICIENCY; URETHRAL DEVELOPMENT;

D O I：

10.1159/000441988

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200-300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgenerational epigenetic impacts. (C) 2015 S. Karger AG, Basel

引用

页码：239 / 259

页数：21

共 192 条

[1] THE HUMAN HOX GENE FAMILY [J].

ACAMPORA, D ;

DESPOSITO, M ;

FAIELLA, A ;

PANNESE, M ;

MIGLIACCIO, E ;

MORELLI, F ;

STORNAIUOLO, A ;

NIGRO, V ;

SIMEONE, A ;

BONCINELLI, E .

NUCLEIC ACIDS RESEARCH, 1989, 17 (24) :10385-10402

[2] Disorders of sex development: effect of molecular diagnostics [J].

Achermann, John C. ;

Domenice, Sorahia ;

Bachega, Tania A. S. S. ;

Nishi, Mirian Y. ;

Mendonca, Berenice B. .

NATURE REVIEWS ENDOCRINOLOGY, 2015, 11 (08) :478-488

[3] The p.G146A and p.P125P Polymorphisms in the Steroidogenic Factor-1 (SF-1) Gene Do Not Affect the Risk for Hypospadias in Caucasians [J].

Adamovic, T. ;

Chen, Y. ;

Thai, H. T. T. ;

Zhang, X. ;

Markljung, E. ;

Zhao, S. ;

Nordenskjold, A. .

SEXUAL DEVELOPMENT, 2012, 6 (06) :292-297

[4] No Association between Maternal Pre-pregnancy Obesity and Risk of Hypospadias or Cryptorchidism in Male Newborns [J].

Adams, Scott V. ;

Hastert, Theresa A. ;

Huang, Yi ;

Starr, Jacqueline R. .

BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, 2011, 91 (04) :241-248

[5] VAMP-7 mediates vesicular transport from endosomes to lysosomes [J].

Advani, RJ ;

Yang, B ;

Prekeris, R ;

Lee, KC ;

Klumperman, J ;

Scheller, RH .

JOURNAL OF CELL BIOLOGY, 1999, 146 (04) :765-775

[6] Ontogeny of androgen receptor and disruption of its mRNA expression by exogenous estrogens during morphogenesis of the genital tubercle [J].

Agras, Koray ;

Willingham, Emily ;

Liu, Benchun ;

Baskin, Laurence S. .

JOURNAL OF UROLOGY, 2006, 176 (04) :1883-1888

[7] AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a clinical diagnosis of androgen insensitivity [J].

Akcay, T. ;

Fernandez-Cancio, M. ;

Turan, S. ;

Gueran, T. ;

Audi, L. ;

Bereket, A. .

ANDROLOGY, 2014, 2 (04) :572-578

[8] Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias [J].

Allali, Slimane ;

Muller, Jean-Baptiste ;

Brauner, Raja ;

Lourenco, Diana ;

Boudjenah, Radia ;

Karageorgou, Vasiliki ;

Trivin, Christine ;

Lottmann, Henri ;

Lortat-Jacob, Stephen ;

Nihoul-Fekete, Claire ;

De Dreuzy, Olivier ;

McElreavey, Ken ;

Bashamboo, Anu .

PLOS ONE, 2011, 6 (10)

[9] MUTATIONS OF THE ANDROGEN RECEPTOR CODING SEQUENCE ARE INFREQUENT IN PATIENTS WITH ISOLATED HYPOSPADIAS [J].

ALLERA, A ;

HERBST, MA ;

GRIFFIN, JE ;

WILSON, JD ;

SCHWEIKERT, HU ;

MCPHAUL, MJ .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1995, 80 (09) :2697-2699

[10] Prevalence of birth defects among infants of gulf war veterans in Arkansas, Arizona, California, Georgia, Hawaii, and Iowa, 1989-1993 [J].

Araneta, MRG ;

Schlangen, KM ;

Edmonds, LD ;

Destiche, DA ;

Merz, RD ;

Hobbs, CA ;

Flood, TJ ;

Harris, JA ;

Krishnamurti, D ;

Gray, GC .

BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, 2003, 67 (04) :246-260

← 1 2 3 4 5 6 7 8 9 10 →