Varma S K, Bloch E, Gondos B, Rossi V, Gunsalus G L, Thysen B
Department of Obstetrics & Gynecology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461.
J Toxicol Environ Health. 1988;25(4):435-51. doi: 10.1080/15287398809531222.
In previous studies we demonstrated reduced fertility, arrested spermatogenesis, and diminished circulating testosterone levels in rats fed 0.03% 2,4-toluenediamine (TDA) for 10 wk. These studies were extended in three experiments by determining TDA effects on androgen-binding protein (rABP) production and on seminiferous tubule structure, and on early changes in testes morphology and spermatogenesis. In the first experiment, rats fed 0.03% TDA for 10 wk showed a 7- to 9-fold increase in rABP content in testicular cytosol or in media of cultured seminiferous tubules, a 4-fold increase in serum rABP, but a two-thirds decrease in epididymal rABP levels. Testes examination by transmission electron microscopy revealed degenerative changes in Sertoli cells with, where present, normal spermatocytes and spermatids. In the second experiment, 0.03% TDA fed for 4, 6, or 8 wk resulted in a doubling of testes/body weight ratios and a highly correlated 2.5- to 2.9-fold increase in seminiferous tubule fluid volume. An approximately 50% decrease in epididymal sperm reserves was found after 6 or 8 wk of TDA exposure. After 10 wk of exposure to 0.03% TDA, testicular weight was the same as in control-fed rats but seminiferous tubule fluid volume was still elevated. These changes in testicular characteristics indicate TDA effects on Sertoli cell function, on RABP release from the testes (and epididymides), and possibly on tubular fluid transport. In the third experiment, rats fed 0.06% TDA for 1 wk showed a 25% decrease in epididymal sperm content, reduced epididymal weight, and minor structural changes in Sertoli cells. After 3 wk of 0.06% TDA feeding, sperm counts were further reduced, and were accompanied by a dramatic increase in testes weight, intense fluid accumulation, and ultrastructural changes in Sertoli cells. No significant changes in serum testosterone levels were noted in the TDA-treated rats. The results of this third experiment demonstrate TDA toxicity on testicular spermatogenesis within 3 wk of TDA feeding. The within 3 wk of TDA feeding. The findings in this study suggest that the early inhibition of spermatogenesis by TDA is mediated through Sertoli cell damage.
在之前的研究中，我们证明了给大鼠喂食0.03%的2,4 - 甲苯二胺（TDA）10周后，其生育能力下降、精子发生停滞以及循环睾酮水平降低。在三项实验中扩展了这些研究，通过确定TDA对雄激素结合蛋白（rABP）产生、生精小管结构、睾丸形态和精子发生早期变化的影响。在第一个实验中，给大鼠喂食0.03% TDA 10周后，睾丸细胞质或培养的生精小管培养基中的rABP含量增加了7至9倍，血清rABP增加了4倍，但附睾rABP水平下降了三分之二。通过透射电子显微镜检查睾丸发现，支持细胞有退行性变化，存在正常的精母细胞和精子细胞。在第二个实验中，给大鼠喂食0.03% TDA 4、6或8周，导致睾丸/体重比翻倍，生精小管液体积高度相关地增加了2.5至2.9倍。在TDA暴露6或8周后，附睾精子储备量大约减少了50%。在暴露于0.03% TDA 10周后，睾丸重量与对照喂养的大鼠相同，但生精小管液体积仍然升高。睾丸特征的这些变化表明TDA对支持细胞功能、睾丸（和附睾）中RABP释放以及可能对小管液运输有影响。在第三个实验中，给大鼠喂食0.06% TDA 1周后，附睾精子含量下降了25%，附睾重量减轻，支持细胞有轻微结构变化。在喂食0.06% TDA 3周后，精子计数进一步减少，同时伴有睾丸重量急剧增加、大量液体蓄积以及支持细胞超微结构变化。在TDA处理的大鼠中未观察到血清睾酮水平有显著变化。第三个实验的结果证明了在喂食TDA 3周内TDA对睾丸精子发生的毒性。在喂食TDA的3周内。本研究的结果表明，TDA对精子发生的早期抑制是通过支持细胞损伤介导的。
