HgsNat (Heparin-alpha;-glucosaminide N-acetyltransferase) gene inactivation affects the lysosomal integrity of epididymal epithelial cells and the morphology of spermatozoa in adult mice

HERMO L; CARVELLI L; MORALES CR; PSHEZHETSKY AV

Cambridge

Conferencia; The Pathobiology of the Lysosome and Lysosomal Diseases Conference 2016; 2016

Zing Conferences

The epididymal epithelium provides a unique environment for sperm maturation controlled in part by the endocytosis of substances from the lumen. Heparan sulfate (HS) is a component of basement membranes and the apical surface of cells. HS is degraded after endocytosis by the action of several enzymes, including HGSNAT. In adult male mice, inactivation of the HgsNat gene shows reduced litter sizes. The objective of this investigation was to determine the morphological abnormalities of HgsNat inactivation on the epithelial cells of the epididymis and epididymal spermatozoa by electron microscopy (EM). In wild type (WT) mice, epithelial principal cells contained small to medium size dense spherical lysosomes. This contrasted HgsNat deficient mice, where numerous large to gigantic empty looking vacuoles of different shapes appeared both supranuclearly and infranuclearly (Figs. 1A,B); immunohistochemical analysis confirmed them as lysosomes. Similar vacuoles were also prominent in basal, halo and myoid cells. Occasional huge cells occupied the mid/basal region of the epithelium which based on morphological criteria were identified as detached clear cells. In the lumen, numerous spermatozoa presented abnormal tails and head shapes (Fig. 1C,D). All of the above observations, although evident in all epididymal regions, were especially prominent in the corpus region. Our results reveal that upon HgsNat inactivation, defects occur to sperm tail formation in the testis, as well as severe alterations to epididymal epithelial cell morphology which may affect sperm maturation. Supported by NSERC and CIHR.