Meistrich Marvin L, Wilson Gene, Shuttlesworth Gladis A, Porter Karen L
M.D. Anderson Cancer Center, Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Reprod Toxicol. 2003 May-Jun;17(3):263-71. doi: 10.1016/s0890-6238(03)00007-8.
Exposure to the nematocide dibromochloropropane (DBCP) has caused prolonged oligo- and azoospermia in men. There are questions regarding the cellular targets resulting in this effect. In this study we characterized an animal model, in which four daily injections of DBCP produced prolonged oligospermia in LBNF(1) rats without any indication of recovery. Between 6 and 20 weeks after DBCP treatment, 70% of seminiferous tubules showed an epithelium with Sertoli cells but no differentiating germ cells. About 20% of tubules contained differentiating germ cells and 10% showed occlusion or major morphologic alterations to Sertoli cells. Since gonadotropin levels and intratesticular testosterone (ITT) concentrations were elevated in the DBCP-treated rats, the failure of spermatogonial development could not have been a result of lack of these hormones. The tubules without differentiating germ cells contained actively proliferating and dividing type A spermatogonia, which underwent apoptosis instead of differentiation. Thus, the target for the damaging effect appears not to be the killing of stem spermatogonia, but the loss of their ability to undergo differentiation. The presence of type A spermatogonia in the atrophic tubules indicates the potential for intervention to restore spermatogenesis.
接触杀线虫剂二溴氯丙烷（DBCP）会导致男性长期少精和无精。关于导致这种效应的细胞靶点存在一些问题。在本研究中，我们对一种动物模型进行了特征描述，在该模型中，每天注射4次DBCP会使LBNF(1)大鼠出现长期少精，且没有任何恢复迹象。在DBCP治疗后的6至20周内，70%的生精小管显示其上皮中有支持细胞，但没有分化的生殖细胞。约20%的小管含有分化的生殖细胞，10%的小管显示支持细胞闭塞或有主要形态学改变。由于DBCP处理的大鼠中促性腺激素水平和睾丸内睾酮（ITT）浓度升高，精原细胞发育失败不可能是这些激素缺乏的结果。没有分化生殖细胞的小管含有活跃增殖和分裂的A型精原细胞，这些细胞发生凋亡而非分化。因此，损伤效应的靶点似乎不是杀死精原干细胞，而是使其失去分化能力。萎缩小管中存在A型精原细胞表明有干预恢复精子发生的潜力。
