Ehmcke Jens, Joshi Bhavika, Hergenrother Scott D, Schlatt Stefan
Department of Cell Biology, University of Pittsburgh School of Medicine, W952 Biomedical Science Towers, 3500 Terrace Street, Pittsburgh 15261, Pennsylvania, USA.
Reproduction. 2007 Jan;133(1):75-83. doi: 10.1530/REP-06-0148.
Testes in aging mammals undergo a variety of age-related changes, such as reduction of size, lower sperm output, an increase in abnormal forms of sperm, and endocrine malfunctions. It has been suggested that the spermatogenic defects are due to loss and dysfunction of spermatogonial stem cells as well as deterioration of the tubule microenvironment. In the present study, we explore the depletion and recovery of spermatogenesis in young (3 month) and old (12 month) mice exposed to cooling, X-irradiation (5 Gy) or cytotoxic treatment using Busulfan (40 mg/kg). We aim to determine a potential age-related change of vulnerability to gonadotoxic treatments by describing the intensity of spermatogenic depletion and the degree of spermatogenic recolonization with qualitative and quantitative parameters on organ weights and histological parameters at two time points (2 weeks, depletion; 6 weeks, recovery). Our data reveal specific acute effects of cooling on multinucleation of germ cells but no other severe injury. Irradiation and Busulfan-treatment exerted the expected depletional wave of germ cells leading to severe testicular injury and spermatogenic failure. The recovery of spermatogenesis occurred in both treatment groups and both age groups to a similar extent. We therefore noted no prominent age-related differences in spermatogenic depletion and recovery in any treatment group. We conclude that in both age groups, the remaining spermatogonial stem cells are capable to induce spermatogenic recovery and the aging tubule microenvironment at 1 year has not become more vulnerable to irradiation, Busulfan-treatment or testicular cooling.
衰老哺乳动物的睾丸会经历各种与年龄相关的变化,如体积减小、精子产量降低、精子异常形态增加以及内分泌功能障碍。有人认为,生精缺陷是由于精原干细胞的丢失和功能障碍以及小管微环境的恶化所致。在本研究中,我们探讨了暴露于低温、X射线照射(5 Gy)或使用白消安(40 mg/kg)进行细胞毒性处理的年轻(3个月)和年老(12个月)小鼠生精的耗竭和恢复情况。我们旨在通过在两个时间点(2周,耗竭;6周,恢复)对器官重量和组织学参数进行定性和定量分析,描述生精耗竭的强度和生精重新定植的程度,以确定与年龄相关的对性腺毒性治疗易感性的潜在变化。我们的数据揭示了低温对生殖细胞多核化的特定急性影响,但没有其他严重损伤。照射和白消安处理引发了预期的生殖细胞耗竭波,导致严重的睾丸损伤和生精失败。两个治疗组和两个年龄组的生精恢复程度相似。因此,我们注意到在任何治疗组中,生精耗竭和恢复在年龄方面没有显著差异。我们得出结论,在两个年龄组中,剩余的精原干细胞都能够诱导生精恢复,并且1岁时衰老的小管微环境对照射、白消安处理或睾丸低温并没有变得更敏感。