Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism
Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism
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DOI：
10.1007/s002400000134
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发表时间：
2000-10-01
影响因子：
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通讯作者：
Chakrabarti, S
中科院分区：
文献类型：
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作者：
Cai, L;Chen, SL;Chakrabarti, S
本文通过对链脲佐菌素 (STZ) 诱导的糖尿病大鼠的睾丸进行临时研究，探讨了内皮素 (ET) 在糖尿病诱导的睾丸损伤中的作用。评估睾丸和附睾重量以及睾丸形态。通过使用常规染色和形态学的光学显微镜以及使用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 技术的凋亡细胞染色来评估细胞死亡。通过半定量逆转录聚合酶链反应（RT-PCR）方法评估内皮素-1（ET-1）mRNA的表达。此外，还研究了混合 ETA 和 ETB 受体拮抗剂波生坦的作用。随访 1 个月时睾丸重量没有显示任何变化，但糖尿病 6 个月后睾丸重量下降。然而，糖尿病大鼠的附睾重量在两个时间段结束时均显着下降。对糖尿病大鼠睾丸的形态学评估显示，生精管直径减小，空睾管数量增加，血管密度增加。此外，糖尿病大鼠中退化的生殖细胞和TUNEL阳性细胞显着高于对照动物。糖尿病动物的这种变化与 ET-1 mRNA 表达增加有关，并且可以通过波生坦治疗来预防。在长期随访中，服用波生坦可以预防糖尿病睾丸中睾丸重量的下降、生精小管直径的减小、血管密度的增加以及退化和凋亡的生殖细胞和空小管的发生率。这些结果表明，ET-1介导的途径可能参与糖尿病的睾丸损伤和生殖细胞凋亡。
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 mts 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.