title: The Genetic and Environmental Factors Underlying Hypospadias.
abstract: 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.
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.|Department of Surgery, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Aurore
authors.initials: A
authors.lastname: Bouty
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Ayers
authors.affiliation: Department of Zoology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pask
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.|Department of Surgery, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Yves
authors.initials: Y
authors.lastname: Heloury
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sinclair
mesh_terms: D000728:Androgens / Q000235:genetics / Q000502:physiology; D000818:Animals; D012734:Disorders of Sex Development / Q000235:genetics; D052244:Endocrine Disruptors; D004777:Environment; D044127:Epigenesis, Genetic; D004967:Estrogens / Q000235:genetics / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology; D020022:Genetic Predisposition to Disease; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007021:Hypospadias / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D010413:Penis / Q000002:abnormalities; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D013737:Testis / Q000254:growth & development; D014521:Urethra / Q000002:abnormalities; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D000728:Androgens; D052244:Endocrine Disruptors; D004967:Estrogens; D053823:Hedgehog Proteins; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors