Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Using mouse models to delineate the importance of beta-catenin/ Wnt signalling in the testis (#352)

Genevieve Kerr 1 , Julia Young 1 , Katja Horvay 1 , Helen E Abud 1 , Kate L Loveland 1
  1. Monash University, Clayton, VIC, Australia
The highly conserved Wnt signalling pathway and its key mediator protein, beta-catenin play essential roles during development and are required for adult tissue homeostasis. Several studies have demonstrated that beta-catenin/Wnt signalling is required for normal spermatogenesis, yet recent controversy has arisen from reports showing differing results.  In some studies, the extent of Wnt activation appears to have been underestimated due to the limited breadth of reporter techniques employed. Previous studies showed that mice with up-regulated Wnt signalling in Sertoli cells exhibit disrupted spermatogenesis, while mice with beta-catenin deletions under control of germ cell- specific Cres identified variable phenotype severities.  We documented several lines of evidence showing that Wnt signalling is active in mitotic and post-mitotic germ cells of adult testes, including: Wnt-reporter activity, observation of nuclear beta-catenin and expression of Wnt downstream targets.  These suggested Wnt signalling may influence first proliferation, then differentiation, as spermatogenesis progresses. We showed that Wnt signalling is essential for normal spermatogenesis using AhCre mouse models with testis-wide perturbations in beta-catenin and the negative regulator, Adenomatous Polyposis Coli [1].  We are currently comparing mouse models in which beta-catenin is selectively deleted in embryonic and early postnatal germ cells (VasaCre and Stra8Cre, respectively) to delineate the importance of germ-cell intrinsic beta-catenin. We are also assessing different beta-catenin mutant alleles to test the role of beta-catenin in cell adhesion vs canonical Wnt signalling in vivo.  Our data highlight that factors such as breeding strategies, strain differences, and Cre recombinase efficiency may influence phenotypic differences observed in Wnt pathway mouse models.  These analyses will reveal how Wnt signalling activity in germ and somatic cells of the testis governs normal spermatogenesis, and indicate how perturbations in Wnt signalling may contribute to some cases of male infertility.