Role of β-Catenin in Post-Meiotic Male Germ Cell Differentiation

Abstract

Though roles of β-catenin signaling during testis development have been well established, relatively little is known about its role in postnatal testicular physiology. Even less is known about its role in post-meiotic germ cell development and differentiation. Here, we report that β-catenin is highly expressed in post-meiotic germ cells and plays an important role during spermiogenesis in mice. Spermatid-specific deletion of β-catenin resulted in significantly reduced sperm count, increased germ cell apoptosis and impaired fertility. In addition, ultrastructural studies show that the loss of β-catenin in post-meiotic germ cells led to acrosomal defects, anomalous release of immature spermatids and disruption of adherens junctions between Sertoli cells and elongating spermatids (apical ectoplasmic specialization; ES). These defects are likely due to altered expression of several genes reportedly involved in Sertoli cell-germ cell adhesion and germ cell differentiation, as revealed by gene expression analysis. Taken together, our results suggest that β-catenin is an important molecular link that integrates Sertoli cell-germ cell adhesion with the signaling events essential for post-meiotic germ cell development and maturation. Since β-catenin is also highly expressed in the Sertoli cells, we propose that binding of germ cell β-catenin complex to β-catenin complex on Sertoli cell at the apical ES surface triggers a signaling cascade that regulates post-meiotic germ cell differentiation.

Paracrine Wnt/β-catenin signaling mediates proliferation of undifferentiated spermatogonia in the adult mouse testis

“…In other studies, germ cell-specific β-catenin CKO mediated by Stra8-iCre, which is expressed in differentiating spermatogonia at the onset of differentiation, did not cause a detectable phenotype (49). In addition, spermatid-specific β-catenin CKO mediated by Prm1-Cre has been shown to cause impaired fertility as a result of reduced sperm counts (50). Another group reported disrupted spermatogenesis in both loss-and gain-of-Wnt signaling function experiments using AhCre (37).…”

Aberrant Wnt/β-Catenin Signaling Pathway in Testis of Azoospermic Men​

“…20,21 The removal of β-catenin in the mouse spermatid increases apoptosis, acrosome defects, abnormal chromatin condensation, and degradation of Sertoli-germ cell junctions in which can lead to infertility. 22 Overexpression of β-catenin leads to uncontrolled proliferation, inhibition of differentiation in Sertoli cells and their function to support germ cells in mice. 23 As a result, relationship of Wnt/β-catenin signaling dysfunction in sertoli, germ cell, and infertility has been confirmed.…”

Flutamide alters the distribution of c-Src and affects the N-cadherin-β-catenin complex in the seminiferous epithelium of adult rat

“…On the other hand, Kerr et al (2014) have recently detected nuclear b-catenin in murine spermatocytes and spermatids and based on mouse model with b-catenin mutation (AhCre Ctnnb1 fl/fl ) proposed Wnt/b-catenin signaling as required at several stages of spermatogenesis. It should be added that other authors also reported that deletion of b-catenin gene or its stabilizing mutation in germ cells caused germ cell deficiency and spermatogenic failure (Kimura et al, 2006;Chang et al, 2011). In contrast, very recently Rivas et al (2014) have showed that conditional deletion of b-catenin in germ cells had no effect on germ cell.…”

“…They form complexes between Sertoli cells at the BTB and between Sertoli cells and elongated spermatids (Vogl et al, 2000). Cadherin-catenin complexes do not only provide mechanical adhesion in the seminiferous epithelium; they also play a crucial role in germ cell morphogenesis and differentiation (Rowlands et al, 2000;Honecker et al, 2004;Chang et al, 2011). In particular, the b-catenin is involved in germ cell maturation by regulating interactions and signaling at the Sertoli cellgerm cell interface.…”

“…In particular, the b-catenin is involved in germ cell maturation by regulating interactions and signaling at the Sertoli cellgerm cell interface. It was established that spermatid-specific deletion of b-catenin resulted in disruption of AJs between Sertoli cells and elongating spermatids, acrosomal defects, increased germ cell apoptosis, and in consequence, reduced sperm count and impaired fertility (Chang et al, 2011). In addition to its role in cell-cell junctions, b-catenin is a key mediator in canonical Wnt signaling pathway, which is known to be important during testicular and ovarian fetal development.…”