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Published on: December 2, 2014
Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice
Kallayanee Chawengsaksophak1, Terje Svingen, Ee Ting Ng
1Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
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.
Insights
Wnt5a is crucial for male sexual development and germ cell migration in mice. Its absence leads to testicular issues and reduced germ cell numbers, impacting reproductive function and clarifying Robinow syndrome.
Area of Science:
- Developmental Biology
- Genetics
- Reproductive Medicine
Background:
- Disorders of sex development (DSDs) arise from disrupted sex determination and differentiation pathways, often impacting reproductive function.
- Many DSD phenotypes remain unexplained at the molecular level despite extensive research into sexual differentiation mechanisms.
Purpose of the Study:
- To investigate the role of Wnt5a in mammalian sexual development.
- To elucidate the molecular underpinnings of Wnt5a's involvement in gonad differentiation and germ cell development.
Main Methods:
- Analysis of Wnt5a expression in mouse testes during gonad differentiation.
- Phenotypic analysis of Wnt5a-null mice, including reproductive organ development and germ cell assessment.
- Investigation of primordial germ cell migration in Wnt5a-deficient embryos.
Main Results:
- Wnt5a is upregulated in male testicular interstitial cells during gonad differentiation.
- Wnt5a deficiency in mice caused testicular hypoplasia and bilateral cryptorchidism.
- Wnt5a-null embryos exhibited reduced gonadal germ cell numbers due to aberrant primordial germ cell migration.
Conclusions:
- Wnt5a plays multiple roles in mammalian reproductive development, including male sexual differentiation and germ cell migration.
- These findings contribute to understanding the etiology of Robinow syndrome, linked to the WNT5A pathway.
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