caa a22 4500 475742869 CHVBK 20180406123504.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s002400000134 doi (NATIONALLICENCE)springer-10.1007/s002400000134 Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism [Elektronische Daten] [Lu Cai, Shali Chen, Terry Evans, Diana Xi Deng, Kallol Mukherjee, Subrata Chakrabarti] This paper explores the role of endothelins (ETs) in diabetes-induced testicular damage by investigating, in a temporal manner, testes from streptozotocin (STZ)-induced diabetic rats. Testicular and epididymal weights and testicular morphology were assessed. Cell death was evaluated by light microscopy using conventional staining and morphology, and by apoptotic cell staining using the Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling (TUNEL) technique. Expression of endothelin-1 (ET-1) mRNA was evaluated by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Furthermore, effects of a mixed ETA and ETB receptor antagonist, bosentan, were studied. Testicular weights did not show any change at 1 month of follow-up, but were decreased after 6 months of diabetes. However, epididymal weights were significantly decreased at the end of both time periods in the diabetic rats. Morphological evaluations of the testes from diabetic rats showed a reduction in seminiferous tubular diameter, an increase in the number of empty testicular tubules and an increase in vascular density. Furthermore, degenerated germ cells and TUNEL-positive cells were significantly higher in diabetic rats than in control animals. The changes in diabetic animals were associated with increased ET-1 mRNA expression and were prevented by bosentan treatment. Administration of bosentan prevented decreased testicular weights, reduced seminiferous tubule diameters, increased vascular densities and incidences of degenerated and apoptotic germ cells and empty tubules in diabetic rats at the long-term follow-up. These results demonstrated that an ET-1 mediated pathway might be involved in testicular injury and germ-cell apoptosis in diabetes. Springer-Verlag Berlin Heidelberg, 2000 Key words Apoptosis nationallicence Diabetic rats nationallicence Enthothelin-1 nationallicence Endothelin blockade nationallicence Spermatogenesis nationallicence Cai Lu Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut Chen Shali Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut Evans Terry Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut Deng Diana Xi Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut Mukherjee Kallol Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut Chakrabarti Subrata Department of Pathology, University of Western Ontario, Dental Sciences Building, London, Ontario, Canada N6A 5C1 e-mail: schakrab@julian.uwo.ca Tel.: +1-519-6633381; Fax: +1-519-6632930, CA aut https://doi.org/10.1007/s002400000134 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002400000134 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cai Lu Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut NATIONALLICENCE 700 1- Chen Shali Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut NATIONALLICENCE 700 1- Evans Terry Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut NATIONALLICENCE 700 1- Deng Diana Xi Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut NATIONALLICENCE 700 1- Mukherjee Kallol Department of Pathology, The University of Western Ontario, London, Ontario, Canada, CA aut NATIONALLICENCE 700 1- Chakrabarti Subrata Department of Pathology, University of Western Ontario, Dental Sciences Building, London, Ontario, Canada N6A 5C1 e-mail: schakrab@julian.uwo.ca Tel.: +1-519-6633381; Fax: +1-519-6632930, CA aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer