Tissue interactions and estrogenic response during human female fetal reproductive tract development
Tissue interactions and estrogenic response during human female fetal reproductive tract development
复制标题
DOI：
10.1016/j.diff.2018.04.002
复制
发表时间：
2018-05-01
期刊：
影响因子：
2.9
通讯作者：
Baskin, Laurence S.
中科院分区：
文献类型：
--
作者：
Cunha, Gerald R.;Kurita, Takeshi;Baskin, Laurence S.
探索了组织相互作用的作用，以确定发育中的人生殖道内的上皮分化是否由小鼠阴道间充质+人输卵管上皮（mVgM+hTubE）组成的组织重组体中的间充质诱导和指定。组织重组体在DES处理的卵巢切除的无胸腺小鼠中生长。在体内生长2-4周后，在人输卵管上皮中表达了几种阴道特异性特征。间充质诱导的影响包括形态学变化以及几种免疫组化标记物的表达。尽管间充质诱导的人输卵管上皮中阴道分化的转变并不完全，但人输卵管上皮中阴道标志物的部分诱导证实了间充质-上皮相互作用在人女性生殖道发育中的重要性。子宫上皮孕酮受体（PGR）和雌激素受体1（ESR 1）的DES诱导在由野生型型或Esr 1 KO小鼠子宫间充质+人胎儿子宫上皮（wt UtM+hUtE和Esr 1 KO UtM+hUtE）。本实验的基本原理是确定DES诱导的PGR和ESR 1是直接通过上皮ESR 1介导的还是间接通过间充质ESR 1介导的（旁分泌机制）。在Esr 1 KP UtM+hUtE组织重组体（缺乏间充质ESR 1）中DES诱导子宫上皮ESR 1和PGR正式消除了旁分泌机制，并证明DES诱导人子宫上皮ESR 1和PGR是通过上皮ESR 1直接介导的。
The role of tissue interactions was explored to determine whether epithelial differentiation within the developing human reproductive tract is induced and specified by mesenchyme in tissue recombinants composed of mouse vaginal mesenchyme + human uterine tubal epithelium (mVgM+hTubE). The tissue recombinants were grown in DES-treated ovariectomized athymic mice. After 2-4 weeks of in vivo growth, several vaginal specific features were expressed in the human tubal epithelium. The mesenchyme-induced effects included morphological change as well as expression of several immunohistochemical markers. Although the mesenchyme-induced shift in vaginal differentiation in the human tubal epithelium was not complete, the partial induction of vaginal markers in human tubal epithelium verifies the importance of mesenchymal-epithelial interactions in development of the human female reproductive tract.In a separate experiment, DES-induction of uterine epithelial progesterone receptor (PGR) and estrogen receptor 1 (ESR1) was explored in tissue recombinants composed of wild-type or Esr1KO mouse uterine mesenchyme + human fetal uterine epithelium (wt UtM+hUtE and Esr1KO UtM+hUtE). The rationale of this experiment was to determine whether DES-induction of PGR and ESR1 is mediated directly via epithelial ESR1 or indirectly (paracrine mechanism) via mesenchymal ESR1. DES-induction of uterine epithelial ESR1 and PGR in Esr1KP UtM+hUtE tissue recombinants (devoid of mesenchymal ESR1) formally eliminates the paracrine mechanism and demonstrates that DES induction of human uterine epithelial ESR1 and PGR is directly mediated via epithelial ESR1.