Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism

This paper explores the role of endothelins (ETs) in diabetes-induced testi cular damage by investigating, in a temporal manner, testes from streptozot ocin (STZ)-induced diabetic rats. Testicular and epididymal weights and tes ticular morphology were assessed. Cell death was evaluated by light microsc opy using conventional staining and morphology, and by apoptotic cell stain ing using the Terminal deoxynucleotidyl transferase-mediated dUTP Nick End- Labeling (TUNEL) technique. Expression of endothelin-1 (ET-1) mRNA was eval uated by a semi-quantitative reverse transcription-polymerase chain reactio n (RT-PCR) method. Furthermore, effects of a mixed ETA and ETB receptor ant agonist, bosentan, were studied. Testicular weights did not show any change at 1 month of follow-up, but were decreased after 6 months of diabetes. Ho wever, epididymal weights were significantly decreased at the end of both t ime periods in the diabetic rats. Morphological evaluations of the testes f rom diabetic rats showed a reduction in seminiferous tubular diameter, an i ncrease in the number of empty testicular tubules and an increase in vascul ar density. Furthermore, degenerated germ cells and TUNEL-positive cells we re significantly higher in diabetic rats than in control animals. The chang es in diabetic animals were associated with increased ET-1 mRNA expression and were prevented by bosentan treatment. Administration of bosentan preven ted decreased testicular weights, reduced seminiferous tubule diameters, in creased vascular densities and incidences of degenerated and apoptotic germ cells and empty tubules in diabetic mts at the long-term follow-up. These results demonstrated that an ET-1 mediated pathway might be involved in tes ticular injury and germ-cell apoptosis in diabetes.