Presence of aberrant epididymal tubules revealing undifferentiated epithelial cells and absence of spermatozoa in a combined neuraminidase-3 and -4 deficient adult mouse model

Abstract

Mammalian neuraminidases are responsible for the removal of sialic acids from glycoproteins and glycolipids and function in a variety of biological phenomena such as lysosomal catabolism and control of cell differentiation and growth. Disruption of Neu3 and Neu4 genes has led to the generation of a mouse model revealing severe neurological disorders. In this study a morphological analysis was performed on the epididymis of 3 month-old neu3 -/- neu4 -/- mice as compared with wild type animals. In neu3 -/- neu4 -/- mice the majority of tubules of the main epididymal duct were large and lined by differentiated epithelial cells, but revealing lysosomal abnormalities in principal and basally located cells. Of particular note was the presence of aberrant epididymal tubules (ATs) juxtaposed next to the main tubules. ATs were small and of different shapes. Layers of myoid cells encased ATs, which they shared with those of the main tubules, but no interstitial space existed between the two. While some ATs were a dense mass of cells, others revealed a distinct lumen devoid of spermatozoa. The latter revealed an undifferentiated epithelium consisting of cuboidal cells and basal cells, with junctional complexes evident at the luminal front. The absence of spermatozoa from the lumen of the ATs suggests that they were not in contact with the main duct, as also implied by the undifferentiated appearance of the epithelium suggesting lack of lumicrine factors. Despite the presence of ATs, the main duct contained ample spermatozoa, as the neu3 -/- neu4 -/- mice were fertile. Taken together the data suggest that absence of Neu3 and Neu4 leads to defects in cell adhesion and differentiation of epithelial cells resulting in aberrant tubular offshoots that fail to remain connected with the main duct. Hence Neu3 and Neu 4 play an essential role in the guidance of epithelial cells during early embryonic formation.