Histopathological and gene expression analysis of mice exposed to diethylstilbestrol

Abstract

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.

Exposure to Diethylstilbestrol During Embryonic and Larval Stages of Medaka Fish (Oryzias latipes) Leads to Sex Reversal in Genetic Males and Reduced Gonad Weight in Genetic Females

“…Accordingly, GSI of these fish were found to be significantly reduced at 4 months of age, proving that the exposure to DES during early stages of development had a long-lasting effect on germ cell proliferation in XX females. A recent report from mouse showed that exposure to DES reduced number of oocytes and spermatogenic cells (26). Previously, also neonatal exposure to DES has been shown to reduce the number of germ and Sertoli cells in testes of rats and mouse (27,28), implying that the signaling pathway that is affected by DES could be well conserved across the species.…”

Effects of Bisphenol A and Diethylstilbestrol on Estrogen Receptor Expression and Male Fertility

“…Hong et al (2010) demonstrated effects of DES on gene expression, but did not provide insight into the injurious effects, or lack thereof, on male fertility. Three other studies revealed a statistically insignificant relationship, or a complete lack of correlation.…”

“…For example, Vitamin A has been linked with re-establishing sperm motility and decreasing the number of malformed sperm following neonatal exposure to BPA (Hendry et al, 2006). Likewise, the use of ginkgo biloba as a possible therapeutic agent for testicular injury caused by DES exposure is currently being studied (Hong et al, 2010).…”

“…It is a known human carcinogen, and is used in some cases as an androgen suppressor in combined antineoplastic therapy (Merck Sharp & Dohme Corp, 2006b). DES was administered to pregnant women in the 1940's-1970's to prevent miscarriages and spontaneous abortions, as well as pre-mature deliveries (Adamsson, Brokken, Paranko, & Toppari, 2008;Hong et al, 2010). Attention to the negative effects on the human endocrine system arose when women exposed to DES neonatally, several years after it was administered to their mothers during pregnancy, developed rare vaginal and uterine cancers at a significantly elevated rate (Hong et al, 2010).…”

“…Exposure to DES has been shown to disrupt steroidogenesis and spermatogenesis in rodents (Cederroth, Schaad, Descombes, Chambon, Vassalli, & Nef, 2007;Hendry, Weaver, Naccarato, & Khan, 2006). Most of this research has been done based on in-utero and neonatal exposure (Hong et al, 2010). While few studies have examined the effects of exposure in adults, such as in the case of antineoplastic uses, it has been shown to drastically increase apoptosis in spermatocytes and spermatids (Ma, Yang, Wang, Shi, & Chen, 2010).…”