CRITICAL COMPONENTS OF TESTICULAR FUNCTION AND SENSITIVITY TO DISRUPTION
CRITICAL COMPONENTS OF TESTICULAR FUNCTION AND SENSITIVITY TO DISRUPTION
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DOI：
10.1095/biolreprod34.1.17
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发表时间：
1986-02-01
影响因子：
3.6
通讯作者：
MEISTRICH, ML
中科院分区：
文献类型：
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作者：
MEISTRICH, ML
有毒物质可以干扰男性生殖系统的许多目标。放射和癌症化疗药物是一类毒素，其灭菌作用可以从睾丸细胞动力学的角度进行定性和定量分析。对这些药物的杀伤最敏感的细胞是快速分裂、分化的精原细胞。经过dna合成阶段的细胞，包括精母细胞、精母细胞和非生殖细胞，通常具有抗性。缓慢循环的精原细胞表现出中等敏感性，但似乎是导致长期少精子症或无精子症和不孕症的关键目标。精子发生的恢复程度和不孕症的持续时间可以在干细胞存活的基础上预测，而与使用的抗肿瘤药物无关。当小鼠干细胞被杀死时，它们的数量和精原上皮的再生几乎立即开始。在人类中，暴露于杀死干细胞的物质后，恢复可能会延迟数年。这是人类干细胞再生和分化调控的结果，其机制尚不清楚。这一规律可以解释物种间对有毒物质敏感性的数量差异。例如，人在受到辐射后的短时间内对精子数量的减少比老鼠敏感得多，但如果有足够的恢复时间，就不会这样。
Toxic agents can interfere with the male reproductive system at many targets. Radiation and cancer chemotherapeutic drugs represent one class of toxins the sterilizing effects of which can be analyzed qualitatively and quantitatively in terms of testicular cell kinetics. The cells most sensitive to killing by these agents are the rapidly dividing, differentiating spermatogonia. Cells past the DNA-synthetic stages, including spermatocytes, spermatids, and nongerminal cells, are generally resistant. The slow cycling stem spermatogonia show an intermediate sensitivity, but appear to be the critical targets for the resulting long-term oligo- or azoospermia and infertility. The extent of recovery of spermatogenesis and the duration of infertility can be predicted on the basis of stem cell survival alone, independent of the antineoplastic agent used. When murine stem cells are killed, regeneration of their number and repopulation of the seminiferous epithelium begin almost immediately. In man, recovery can be delayed for years after exposure to agents that kill stem cells. This is a result of the regulation of stem cell regeneration and differentiation in man, the mechanisms of which are unknown. This regulation can explain quantitative differences in interspecies sensitivities to toxic agents. For example, man is much more sensitive than the mouse to reduction in sperm count by radiation at short times after exposure, but not when sufficient recovery times are allowed.