Glasser S R, Mulholland J
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Microsc Res Tech. 1993 Jun 1;25(2):106-20. doi: 10.1002/jemt.1070250204.
Useful knowledge of the mechanisms which regulate ovoreceptivity and implantation remains elusive in spite of increasing efforts to apply the technology of biochemistry and to a lesser extent, cellular and molecular biology to the analysis of the problem. Existing models used to analyze interactions of the blastocyst and endometrial cells of the uterus have been unable to account for nongenotypic embryonic losses, particularly those following in vitro fertilization and embryo transfer. Separation of endometrial uterine epithelial (UE) and uterine stromal (US) cells was used to demonstrate that each cell type responds independently and interdependently to the same regulatory signals. Cultured by classical techniques UE cells proved unable to respond to steroid hormone signals. For this reason UE cell cultures could not be used to develop an experimental cell system that mimicked growth and development of UE cells in utero. The failure of classical UE cell cultures derived from their inability to maintain epithelial cell polarity. Polarity, the spatial asymmetry of plasma membrane domains, is intrinsic to the structure and function of an epithelial cell. Apical and basolateral surfaces have different lipid and protein compositions which are correlates of the special functions of that epithelial cell. As epithelial cells differentiate they must, in response to regulatory cues, direct the flux of membrane components moving into and out of each surface in order to establish the polarity characteristic of each stage specific expression. The acquisition of receptivity by the apical surface of the UE cell may be considered to be such a special function. To prove this hypothesis polarized cultures of primary UE cells had to be developed that were hormonally responsive. Such an experimental cell system could serve as a model for in vitro implantation. This essay describes such a culture system in which blastocysts cocultured with UE cells in the presence of estrogen, will as predicted, fail to attach. This polarized UE cell system provides a functional in vitro model to study ovoreceptivity. It is now feasible to initiate studies of hormonal regulation of the composition and function of UE cell plasma membranes as they reflect the nonreceptive, receptive, and refractory nature of its apical surface.
尽管人们越来越努力地运用生物化学技术,以及在较小程度上运用细胞和分子生物学技术来分析这一问题,但调节卵子接受性和着床的机制的有用知识仍然难以捉摸。用于分析胚泡与子宫子宫内膜细胞相互作用的现有模型无法解释非基因型胚胎损失,特别是体外受精和胚胎移植后的那些损失。分离子宫内膜子宫上皮(UE)细胞和子宫基质(US)细胞用于证明每种细胞类型对相同的调节信号有独立和相互依赖的反应。通过经典技术培养的UE细胞被证明无法对类固醇激素信号作出反应。因此,UE细胞培养不能用于开发一个模拟子宫内UE细胞生长和发育的实验细胞系统。经典UE细胞培养失败是因为它们无法维持上皮细胞极性。极性,即质膜结构域的空间不对称性,是上皮细胞结构和功能所固有的。顶端和基底外侧表面具有不同的脂质和蛋白质组成,这与该上皮细胞的特殊功能相关。随着上皮细胞分化,它们必须响应调节信号,引导膜成分进出每个表面的流动,以建立每个阶段特异性表达的极性特征。UE细胞顶端表面获得接受性可被认为是这样一种特殊功能。为了证明这一假设,必须开发出对激素有反应的原代UE细胞的极化培养物。这样一个实验细胞系统可以作为体外着床的模型。本文描述了这样一种培养系统,在雌激素存在的情况下,与UE细胞共培养的胚泡将如预期的那样无法附着。这个极化的UE细胞系统提供了一个功能性的体外模型来研究卵子接受性。现在开始研究UE细胞质膜的组成和功能的激素调节是可行的,因为它们反映了其顶端表面的非接受性、接受性和不应性性质。