The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero

Monica M Laronda, Kenji Unno, Lindsey M. Butler, Takeshi Kurita*

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow-up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenoses are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models that can be used to study the development of DES-induced anomalies, focusing on cervical and vaginal adenoses, and discusses their molecular pathogenesis.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalDifferentiation
Volume84
Issue number3
DOIs
StatePublished - Oct 1 2012

Keywords

  • Adenosis
  • Diethylstilbestrol
  • P63
  • TRP63
  • Vaginal adenocarcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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