In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system

Karen Block, Andrew Kardana, Peter Igarashi, Hugh S. Taylor

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

Diethylstilbestrol (DES) was widely used to treat pregnant women through 1971. The reproductive tracts of their female offspring exposed to DES in utero are characterized by anatomic abnormalities. Here we show that DES administered to mice in utero produces changes in the expression pattern of several Hox genes that are involved in patterning of the reproductive tract. DES produces posterior shifts in Hox gene expression and homeotic anterior transformations of the reproductive tract. In human uterine or cervical cell cultures, DES induces HOXA9 or HOXA10 gene expression, respectively, to levels approximately twofold that induced by estradiol. The DES-induced expression is not inhibited by cyclohexamide. Estrogens are novel morphogens that directly regulate the expression pattern of posterior Hox genes in a manner analogous to retinoic acid regulation of anterior Hox genes. Alterations in HOX gene expression are a molecular mechanism by which DES affects reproductive tract development. Changes in Hox gene expression are a potential marker for the effects of in utero drug use that may become apparent only at late stages of development.

Original languageEnglish (US)
Pages (from-to)1101-1108
Number of pages8
JournalFASEB Journal
Volume14
Issue number9
StatePublished - Jun 24 2000

Keywords

  • Estrogens
  • Fetal development
  • Genes
  • Homeobox
  • Teratogens

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Block, K., Kardana, A., Igarashi, P., & Taylor, H. S. (2000). In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system. FASEB Journal, 14(9), 1101-1108.