2. Academic Validation
  3. The Genetic and Environmental Factors Underlying Hypospadias

The Genetic and Environmental Factors Underlying Hypospadias

  • Sex Dev. 2015;9(5):239-259. doi: 10.1159/000441988.
Aurore Bouty # 1 2 3,  Katie L Ayers # 1 3,  Andrew Pask 4,  Yves Heloury 1 2 3,  Andrew H Sinclair 1 3
Affiliations

Affiliations

  • 1 Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.
  • 2 Department of Surgery, Royal Children's Hospital, University of Melbourne, Melbourne, Vic., Australia.
  • 3 Department of Paediatrics, University of Melbourne, Melbourne, Vic., Australia.
  • 4 Department of Zoology, University of Melbourne, Melbourne, Vic., Australia.
  • # Contributed equally.
PMID: 26613581 DOI: 10.1159/000441988
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.

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