Effects of exogenous testosterone on testicular function during the chronic phase of spinal cord injury: Dose effects on spermatogenesis and Sertoli cell and sperm function
Effects of exogenous testosterone on testicular function during the chronic phase of spinal cord injury: Dose effects on spermatogenesis and Sertoli cell and sperm function
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DOI：
10.1080/10790268.2004.11753731
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发表时间：
2004-01-01
影响因子：
1.7
通讯作者：
Jetko, JA
中科院分区：
文献类型：
--
作者：
Huang, HFS;Li, MT;Jetko, JA
前言：外源性睾酮已被证明可以减轻大鼠脊髓损伤(SCI)相关的生精退化。本实验观察了外源性睾酮对慢性脊髓损伤大鼠睾丸和精子功能的影响。方法：慢性脊髓损伤大鼠皮下埋植睾酮硅胶胶囊。Northern杂交检测睾丸支持细胞和生殖细胞特异性转录本的水平。用Western印迹和免疫组织化学方法分别检测睾丸组织中环磷酸腺苷反应元件调节剂(CREM)的蛋白水平和细胞定位。用流式细胞仪检测精子存活率和线粒体潜能。结果：8只未经治疗的脊髓损伤大鼠中，有7只发生了自发性生精。尽管外源性睾酮恢复了所有脊髓损伤大鼠的完全生精作用，但退化的生精上皮仍保留在这些大鼠30%至70%的肾小管横断面上。这些效应与生殖细胞特异性mRNA转录本对外源性睾酮的反应改变以及CREM的异常细胞分布有关。未经治疗的脊髓损伤大鼠的精子活力、存活率和线粒体潜力降低。10 cm TC可使假手术组和SCI组大鼠精子活力下降，但能恢复SCI大鼠的精子存活率和线粒体潜能。结论：SCI大鼠慢性损伤时给予外源性睾酮不能促进生精功能的恢复。减数分裂后生精分化的异常可能与这些效应有关，也可能与SCI慢性期产生形态和/或功能异常的精子有关。
Introduction: Exogenous testosterone has been shown to attenuate spinal cord injury (SCI)-related regression of spermatogenesis in the rat. The current experiment investigated the effects of exogenous testosterone in testicular and sperm functions in the rat during the chronic phase of SCI.Methods: Chronic SCI rats were given subcutaneous implants of testosterone-filled silastic capsules (TC). Northern blot cDNA hybridization was used to measure testicular levels of Sertoli cell- and germ cell-specific transcripts. Western blot and immunohistochemistry were used to determine protein level and cellular localization, respectively, of cyclic adenosine monophosphate-responsive element modulator (CREM) in the testes. Flow cytometry was used to determine sperm viability and mitochondrial potential.Results: Spontaneous restoration of spermatogenesis occurred in 7 of the 8 untreated SCI rats. Although exogenous testosterone restored complete spermatogenesis in all SCI rats, regressed seminiferous epithelium remained in 30% to 70% of tubular cross sections in these rats. These effects were associated with altered responses of germ cell-specific mRNA transcripts to exogenous testosterone, and abnormal cellular distribution of CREM. Sperm of untreated SCI rats exhibited lowered motility, viability, and mitochondrial potential. Implantation of 10 cm of TC worsened sperm motility in sham control and SCI rats, but restored sperm viability and mitochondrial potential in SCI rats.Conclusion: Administration of exogenous testosterone to SCI rats during the chronic phase of injury failed to facilitate spermatogenic restoration over that achieved in untreated SCI rats. Abnormalities in postmeiotic spermatogenic differentiation could contribute to these effects, and perhaps the production of sperm with abnormal morphology and/or functions during the chronic phase of SCI.