Laboratory of Biochemistry and Molecular Biology, College of Biological Sciences, China Agricultural University, Beijing 100094, PR China.
Toxicol Mech Methods. 2010 Mar;20(3):105-11. doi: 10.3109/15376510903572631.
The estrogenic compound diethylstilbestrol (DES) has been widely studied to understand its potential involvement in endocrine function and carcinogenesis. This study examined the influence of DES on adult mice by histopathological analysis and studied the gene expression changes using mRNA differential display. Pathological changes in the mice following DES exposure included testicular atrophy, ovarian and hepatic fibrosis, and reduced numbers of mature oocytes and spermatogenic cells. Other pathological changes, such as cirrhosis of the liver, were also found. To elucidate the molecular mechanism underlying these effects, we used mRNA differential display to analyze changes in gene expression following DES exposure. In total, 20 genes were differentially expressed in liver, kidney, ovary, uterus, and testis. All putative target genes were validated by QRT-PCR. The study provides evidence that DES has an acute effect on gene expression. The results may facilitate the discovery of the genotoxic mechanism of DES and allow one to discover new DES-responsive genes.
已广泛研究雌激素化合物己烯雌酚(DES),以了解其在内分泌功能和致癌作用中的潜在作用。本研究通过组织病理学分析检查 DES 对成年小鼠的影响,并使用 mRNA 差异显示研究基因表达变化。DES 暴露后小鼠的病理变化包括睾丸萎缩、卵巢和肝纤维化以及成熟卵母细胞和精原细胞数量减少。还发现了其他病理变化,如肝硬化。为了阐明这些影响的分子机制,我们使用 mRNA 差异显示分析 DES 暴露后基因表达的变化。总共在肝脏、肾脏、卵巢、子宫和睾丸中鉴定了 20 个差异表达的基因。所有假定的靶基因均通过 QRT-PCR 进行验证。该研究提供了 DES 对基因表达具有急性影响的证据。研究结果可能有助于发现 DES 的遗传毒性机制,并发现新的 DES 反应基因。