Histopathological and gene expression analysis of mice exposed to diethylstilbestrol

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.