Fusion failure of dense-cored proacrosomal vesicles in an inducible mouse model of male infertility

Abstract

The acrosome is a specialized secretory vesicle located in the head of spermatozoa and has an essential role during fertilization. This organelle and the sperm nucleus have aberrant morphologies in forms of male infertility in humans (teratozoospermia), often associated with poor motility (asthenoteratozoospermia). To further our understanding of the aetiology of these conditions, we have performed a pathological investigation of a model of asthenoteratozoospermia that can be induced in mice by N-butyldeoxynojirimycin (NB-DNJ). We have found that, in mice treated with NB-DNJ, instead of an acrosome forming over the round spermatid nucleus, multivesicular bodies (MVB) accumulate in the vicinity of this nucleus. Electron microscopy has revealed that proacrosomic vesicles or granules (PAG) secreted during the Golgi phase of spermiogenesis do not fuse together to form an acrosomic vesicle, but rather attach transiently to the spermatid nucleus. Immunocytochemistry has shown that acrosomal membrane proteins and cytosolic acrosome-associated proteins are redirected to MVB in affected testes, whereas glycoproteins originating in the dense core of the PAG are degraded. Thus, the major effect of NB-DNJ is to inhibit membrane fusion of Golgi-derived secretory vesicles destined for acrosome formation, raising the possibility that these vesicles are critically affected in forms of (astheno)teratozoospermia.