Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice

Chawengsaksophak, Kallayanee, Svingen, Terje, Ng, Ee Ting, Epp, Trevor, Spiller, Cassy M., Clark, Charlotte, Cooper, Helen and Koopman, Peter (2012) Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice. Biology of Reproduction, 86 1: 1-12. doi:10.1095/biolreprod.111.095232


Author Chawengsaksophak, Kallayanee
Svingen, Terje
Ng, Ee Ting
Epp, Trevor
Spiller, Cassy M.
Clark, Charlotte
Cooper, Helen
Koopman, Peter
Title Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice
Formatted title
Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice
Journal name Biology of Reproduction   Check publisher's open access policy
ISSN 0006-3363
1529-7268
Publication date 2012-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1095/biolreprod.111.095232
Open Access Status Not yet assessed
Volume 86
Issue 1
Start page 1
End page 12
Total pages 12
Place of publication Madison, WI, United States
Publisher Society for the Study of Reproduction
Language eng
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.
Formatted abstract
Disruptions in the regulatory pathways controlling sex determination and differentiation can cause disorders of sex development (DSD), 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 DSD 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 up-regulated 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 aetiology of Robinow syndrome (OMIM 268310), a disease previously linked to the WNT5A pathway.
Keyword Primordial germ cells
Testis
Robinow syndrome
Wnt5a
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 7 September 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 34 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 34 times in Scopus Article | Citations
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Created: Tue, 13 Sep 2011, 21:16:04 EST by Dr Kallayanee Chawengsaksophak on behalf of School of Biomedical Sciences