Persistent gene expression in vagina exposed neonatally to DES

Developmental exposure to diethylstilbestrol, and expression and phosphorylation status of IL-1 and IGF-I signaling pathway components

2004 Study Abstract

Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces carcinogenesis in human and laboratory animals.

In mice, neonatal DES treatment induces persistent proliferation and keratinization of the vaginal epithelium, even in the absence of the ovaries, resulting in cancerous lesions later in life.

To understand the mechanisms underlying this persistent cell proliferation and differentiation, we characterized the gene expression patterns in the neonatally DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR.

  • We found that genes related to cellular signaling, which are candidates for mediating the persistent proliferation and differentiation, were altered, and genes related to the immune system were decreased in the neonatally DES-exposed mouse vagina.
  • We also noted high expression of interleukin-1 (IL-1)-related genes accompanied by phosphorylation of JNK1.
  • In addition, expression IGF-I and its binding proteins was modulated and led to phosphorylation of IGF-I receptor and Akt, which is one of the downstream factors of IGF-I signaling.

This led us to characterize the expression as well as the phosphorylation status of IL-1 and IGF-I signaling pathway components which may activate the phosphorylation cascade in the vagina of mice exposed neonatally to DES. These findings give insight into persistent activation in the vagina of mice exposed neonatally to DES.

Sources and more information
  • Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol, Journal of molecular endocrinology, NCBI PubMed PMID: 15171707, 2004 June.
  • The process of gene expression transcription featured image credit Genome Research Limited.
DES DIETHYLSTILBESTROL RESOURCES

Have your say ! Share your views