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

K Block1, A Kardana, P Igarashi

  • 1Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 2, 2000
PubMed

Insights

Diethylstilbestrol (DES) exposure in utero alters Hox gene expression, causing reproductive tract abnormalities in offspring. These changes in HOX gene patterns may serve as a marker for developmental effects of in utero drug exposure.

Area of Science:

  • Developmental biology
  • Endocrinology
  • Genetics

Background:

  • Diethylstilbestrol (DES) was prescribed to pregnant women until 1971, leading to reproductive abnormalities in female offspring.
  • Hox genes are crucial for the development and patterning of the reproductive tract.

Purpose of the Study:

  • To investigate the molecular mechanisms by which in utero DES exposure affects reproductive tract development.
  • To determine if DES alters Hox gene expression patterns in exposed offspring.

Main Methods:

  • DES was administered to pregnant mice to assess effects on offspring reproductive tract development and Hox gene expression.
  • Human uterine and cervical cell cultures were used to study DES effects on HOXA9 and HOXA10 gene expression.

Main Results:

  • In utero DES exposure in mice resulted in posterior shifts of Hox gene expression and anterior homeotic transformations of the reproductive tract.
  • DES significantly increased HOXA9 and HOXA10 gene expression in human cell cultures, an effect not blocked by cyclohexamide.
  • Estrogen acts as a morphogen, directly regulating posterior Hox gene expression.

Conclusions:

  • Altered HOX gene expression is a key molecular mechanism underlying DES-induced reproductive tract malformations.
  • Changes in Hox gene expression may serve as a biomarker for developmental effects of in utero drug exposure, potentially manifesting later in life.

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