Alterations in the Testis and Epididymis Associated With Loss of Function of the Cystatin-Related Epididymal Spermatogenic (CRES) Protein

Cystatin-related epididymal spermatogenic protein (GRES) or cystatin 8 (Cst8 gene) is a member of the cystatin superfamily of cysteine protease inhibitors. It differs from typical cystatins because it lacks consensus sites for cysteine protease inhibition and exhibits reproductive-specific expression. In the present study, we examined GRES expression within the testes, efferent ducts, and epididymides of normal mice by light microscope immunolocalizaton. Alterations to these tissues in male mice lacking the Cst8 gene (Cst8(-/-)) were also characterized by histomorphometry and electron microscopy. In the normal testis, GRES was localized exclusively in mid and late elongating spermatids. In the efferent ducts, GRES was localized to the apical region of the epithelial cells suggestive of localization in the endosomes. In the initial segment of the epididymis, principal cells showed supranuclear and lumina! reactions. In the cauda region, CRES was present exclusively as aggregates in the lumen and was detected in clear cells. Compared with wild-type mice (Cst8(+/+)), older (10-12 months) Cst8(-/-) mice had modest but statistically