title: Regulated Wnt/beta-catenin signaling sustains adult spermatogenesis in mice.
abstract: The importance of Wnt signaling for postnatal testis function has been previously studied in several mouse models, with chronic pathway disruption addressing its function in Sertoli cells and in postmeiotic germ cells. While chronic beta-catenin deletion in Sertoli cells does not profoundly affect testis development, new data indicate that Wnt signaling is required at multiple stages of spermatogenesis. We used two mouse models that allow acute disruption of Wnt signaling to explore the importance of regulated Wnt pathway activity for normal germ cell development in adult male mice. Short-term induction of mutations in Adenomatous polyposis coli (Apc) and beta-catenin (Ctnnbl), which increase and decrease Wnt signaling levels, were generated in AhCre Apc(fl/fl) and AhCre Ctnnb1(fl/fl) mice, respectively. Each exhibited a distinct phenotype of disrupted spermatogenesis that was evident within 24 h and persisted for up to 4 days. Outcomes included germ cell apoptosis and rapid loss and altered blood-testis barrier protein distribution and morphology. The functional significance of nuclear localized beta-catenin protein in spermatocytes and round spermatids, indicative of active Wnt signaling, was highlighted by the profound loss of postmitotic germ cells in both models. Developmentally regulated Wnt signaling mediators identified through transcriptional profiling of wild-type and AhCre Ctnnb1(fl/fl) mouse testes identified Wnt receptors (e.g., Fzd4) and ligands (e.g., Wnt3, Wnt3a, Wnt5b, Wnt7a, and Wnt8b). This demonstration that Wnt signaling control is essential for adult spermatogenesis supports the growing understanding that its disruption may underpin certain cases of male infertility.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Genevieve E
authors.initials: GE
authors.lastname: Kerr
authors.forename: Julia C
authors.initials: JC
authors.lastname: Young
authors.forename: Katja
authors.initials: K
authors.lastname: Horvay
authors.forename: Helen E
authors.initials: HE
authors.lastname: Abud
authors.forename: Kate L
authors.initials: KL
authors.lastname: Loveland
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D017491:Genes, APC; D005854:Germ Cells / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013087:Spermatids / Q000166:cytology / Q000502:physiology; D013090:Spermatocytes / Q000166:cytology / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051176:beta Catenin
keywords: APC; germ cells; mouse models; spermatids; spermatocytes; testis