Periódicos Brasileiros em Medicina Veterinária e Zootecnia

p. 206-206

Complex alterations in structure and function associated with loss of function of specific genes/proteins in the male reproductive system

Hermo, LSmith, C. E

Spermatogenesis is a complex process of cellular and subcellular interactions implicating a plethora of proteins carrying out many diverse functions and involving the production and differentiation of sperm that ultimately mature in the epididymis. Over the past 20 years we have investigated the functions of many proteins with specific roles in male reproduction using knockout mouse models. Cathepsin A (PPCA) is a lysosomal carboxypeptidase highly expressed in Sertoli cells, Leydig cells and macrophages in the testis and in specific cell types and regions of the epididymis. In PPCA-deficient mice, both Sertoli and germ cells appear normal, but there are significant decreases in tubular diameters with age. Major abnormalities in the testis involve macrophages which significantly change in number, size and appearance. Epididymal epithelial cells are vastly altered in morphology, coincident with significant reductions in shape and size of tubules and dependent on specific cell type and regions of the epididymis. Electron microscope analyses reveal grossly enlarged lysosomes which at times engorge the entire cell cytoplasm. Despite a 70% reduction in sperm counts and major increases in slow moving and static sperm, PPCA-/- mice are fertile albeit with reduced litter sizes. β-hexosaminidase (Hex) is a lysosomal enzyme formed from α and β subunits comprising the enzymes Hex A (αβ) and Hex B (ββ). Hex is highly expressed in Sertoli cells and in a cell type-region specific manner in the epididymis. Interestingly, mice deficient in the α or β subunit reveal no apparent abnormalities in the testis, but epididymal epithelial cells have grossly abnormal lysosomes, which dependent on the missing subunit show cell type and region specific differences. Nevertheless, despite the major disruption in the epididymis and reduced sperm counts, young mice are still fertile...(AU)

Resumo apresentado no III International Symposium Animal Biology of Reproductive, São Pedro, SP, 22-24 out. 2010

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