Loss of Wnt5a Disrupts Primordial Germ Cell Migration and Male Sexual Development in Mice

Kallayanee Chawengsaksophak, Terje Svingen, Ee Ting Ng, Trevor Epp, Cassy M. Spiller, Charlotte Clark, Helen Cooper, Peter Koopman

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Disruptions in the regulatory pathways controlling sex determination and differentiation can cause disorders of sex development, often compromising reproductive function. Although extensive efforts have been channeled into elucidating the regulatory mechanisms controlling the many aspects of sexual differentiation, the majority of disorders of sex development phenotypes are still unexplained at the molecular level. In this study, we have analyzed the potential involvement of Wnt5a in sexual development and show in mice that Wnt5a is male-specifically upregulated within testicular interstitial cells at the onset of gonad differentiation. Homozygous deletion of Wnt5a affected sexual development in male mice, causing testicular hypoplasia and bilateral cryptorchidism despite the Leydig cells producing factors such as Hsd3b1 and Insl3. Additionally, Wnt5a-null embryos of both sexes showed a significant reduction in gonadal germ cell numbers, which was caused by aberrant primordial germ cell migration along the hindgut endoderm prior to gonadal colonization. Our results indicate multiple roles for Wnt5a during mammalian reproductive development and help to clarify further the etiology of Robinow syndrome (OMIM 268310), a disease previously linked to the WNT5A pathway.
Original languageEnglish
Article number4
JournalBiology of Reproduction
Volume86
Issue number1
Pages (from-to)1-12
ISSN0006-3363
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • bilateral cryptorchidism
  • cell migration
  • gonadal colonization
  • OMIM 268310
  • reproductive development
  • sexual development
  • Robinow syndrome congenital disease, genetic disease genetics
  • testicular hypoplasia reproductive system disease/male
  • Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae [86375] mouse common embryo male strain-CD1, strain-B6
  • mouse Amh gene [Muridae] expression
  • mouse Cyp11a1 gene [Muridae] expression
  • mouse Ddx4 gene [Muridae] expression
  • mouse Hsd3b1 gene [Muridae] expression
  • mouse Insl3 gene [Muridae] expression
  • mouse Nr5a1 gene [Muridae] expression
  • mouse Pou5f1 gene [Muridae] expression
  • mouse Rps29 gene [Muridae] expression
  • mouse Sdha gene [Muridae] expression
  • mouse Sox9 gene [Muridae] expression
  • mouse Wnt5a gene [Muridae] expression, loss of function, up-regulation, deletion
  • 02506, Cytology - Animal
  • 03502, Genetics - General
  • 03506, Genetics - Animal
  • 14004, Digestive system - Physiology and biochemistry
  • 16504, Reproductive system - Physiology and biochemistry
  • 16506, Reproductive system - Pathology
  • 17006, Endocrine - Gonads and placenta
  • 25502, Development and Embryology - General and descriptive
  • 25503, Development and Embryology - Pathology
  • Biochemistry and Molecular Biophysics
  • Reproduction
  • endoderm embryonic structure
  • germ cell reproductive system
  • gonadal cell reproductive system
  • hindgut digestive system
  • Leydig cell reproductive system
  • Development
  • Genetics
  • Molecular Genetics
  • Reproductive System

Cite this

Chawengsaksophak, K., Svingen, T., Ng, E. T., Epp, T., Spiller, C. M., Clark, C., Cooper, H., & Koopman, P. (2012). Loss of Wnt5a Disrupts Primordial Germ Cell Migration and Male Sexual Development in Mice. Biology of Reproduction, 86(1), 1-12. [4]. https://doi.org/10.1095/biolreprod.111.095232