Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis
Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis
复制标题
白消安对小鼠附睾形态产生毒性作用并抑制ZO-1和波形蛋白的表达
DOI：
10.1042/bsr20171059
复制
发表时间：
2017-12-22
影响因子：
4
通讯作者：
Xiong, Chengliang
中科院分区：
文献类型：
--
作者：
Fang, Fang;Ni, Ke;Xiong, Chengliang
白消安是目前用作抗癌药物和制备无精子症动物模型的烷烃磺酸盐，因为它选择性地破坏睾丸中分化的精原细胞。然而，目前很少有研究关注白消安治疗对附睾的确切影响。本研究探讨白消安对小鼠附睾形态学及血-附睾屏障的影响。我们对小鼠单次注射白消安，并在不同时间点检测其效果。结果表明白消安对附睾的形态结构和功能均有毒性作用。此外，白消安治疗下调波形蛋白和闭锁小带-1（ZO-1）在mRNA和蛋白水平的附睾表达。此外，白消安治疗后，头部和尾部区域的总雄激素受体（AR）水平升高，而雌激素受体-α（ER-α）水平降低，这可能继发于睾丸损伤。总之，我们的研究描述了白消安给药对小鼠附睾的影响，也提供了一个潜在的理解化疗相关的附睾缺陷所产生的男性不育症。
Busulfan is an alkane sulphonate currently used as an anticancer drug and to prepare azoospermic animal models, because it selectively destroys differentiated spermatogonia in the testes. However, few studies have focussed on the exact effects of busulfan treatment on the epididymis currently. The present study assessed the effect of busulfan on epididymal morphology and the blood–epididymis barrier in mice. We treated mice with a single injection of busulfan and detected the effect at different time points. We showed that busulfan was toxic to the morphological structure and function of the epididymis. Furthermore, busulfan treatment down-regulated the epididymal expression of vimentin and zonula occludens-1 (ZO-1) at the mRNA and protein levels. In addition, there was an increase in total androgen receptor (AR) levels, whereas the estrogen receptor-α (ER-α) levels were reduced, both in the caput and cauda regions after busulfan treatment, which may be secondary to the testicular damage. In conclusion, our study describes the effects of busulfan administration on the mouse epididymis and also provides a potential understanding of male infertility arising from chemotherapy-related defects in the epididymis.