Kurita T
Differentiation 2011 Oct;82(3):117-26
PMID: 21612855
子宮と頚管、そして腟はどのように分化しているのか議論があったが、「腟の頭側2/3まではミューラー管由来、それより尾側は泌尿生殖洞由来」で決着がついたようだ。ウォルフ管はミューラー管のガイドのみとしての機能が強い。腟の上皮のマーカーにはK14, PR, P63などがある。このうち、Diethylstilbestrol (DES)を妊娠中の母親に投与するとその子の腟や子宮に発生学的な異常が生じる。それが頸管や腟の腺疾患と明細胞腺癌、そして子宮の扁平上皮化生である。これはDiethylstilbestrol (DES)投与によりP63の発現が変わっていることで説明できる。ジエチルスチルベストロール(Diethylstilbestrol)は、かつて流産防止剤などに用いられた合成女性ホルモンで、現在は使われていない。畜産分野でも過去に使われていたようだ。
Abstract
In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences.