Kim J J, Jaffe R C, Fazleabas A T
Department of Obstetrics and Gynecology, University of Illinois, Chicago 60612-7313, USA.
Hum Reprod. 1999 Dec;14 Suppl 2:45-55. doi: 10.1093/humrep/14.suppl_2.45.
One of the most remarkable processes associated with the establishment of pregnancy in the primate is the process of decidualization. This transformation of a stromal fibroblast to a fully differentiated decidual cell is required for implantation and embryo survival in early pregnancy. Although the morphological and biochemical characteristics of the primate decidual cell have been extensively studied, the precise cellular, biochemical and molecular signals required for this transformation have yet to be elucidated. During decidualization, stromal cells first proliferate and then differentiate. Based on our extensive in-vivo and ongoing in-vitro studies, we have suggested that the process of decidualization in the baboon can be divided into two distinct phases. The initial proliferative phase is characterized by the expression of the cytoskeletal protein alpha smooth muscle actin (alphaSMA) in the stromal fibroblasts and is independent of the presence of the conceptus. The second phase of differentiation is characterized by the expression of insulin-like growth factor binding protein-1 (IGFBP-1) and the down-regulation of alphaSMA in the decidualized stromal fibroblast. The expression of IGFBP-1 is dependent on the presence of the conceptus in vivo and is regulated by hormones and cAMP in vitro. We have postulated that, during the initial phase of stromal cell differentiation, alphaSMA expression is regulated by the interaction between stromal cell integrins with the secreted extracellular matrix proteins (ECM). In response to pregnancy a trophoblast 'factor', mediated by cAMP signal transduction, induces IGFBP-1 expression in decidualizing stromal fibroblasts. This induction of IGFBP-1 is associated with the disappearance of alphaSMA and de-novo protein synthesis. Our comparative studies suggest that the process of decidualization in the human and baboon involve similar mechanisms. However, the metabolic pathways required for decidualization in the two species appear to differ in their degree of sensitivity to external stimuli. This review focuses on the cellular events that may potentially regulate decidualization in the primate and its role in regulating trophoblast migration.
在灵长类动物中，与妊娠建立相关的最显著过程之一是蜕膜化过程。这种基质成纤维细胞向完全分化的蜕膜细胞的转变是早期妊娠着床和胚胎存活所必需的。尽管对灵长类蜕膜细胞的形态和生化特征进行了广泛研究，但这种转变所需的精确细胞、生化和分子信号仍有待阐明。在蜕膜化过程中，基质细胞首先增殖然后分化。基于我们广泛的体内研究和正在进行的体外研究，我们认为狒狒的蜕膜化过程可分为两个不同阶段。初始增殖阶段的特征是基质成纤维细胞中细胞骨架蛋白α平滑肌肌动蛋白（αSMA）的表达，且与孕体的存在无关。分化的第二阶段的特征是蜕膜化基质成纤维细胞中胰岛素样生长因子结合蛋白-1（IGFBP-1）的表达以及αSMA的下调。IGFBP-1的表达在体内依赖于孕体的存在，在体外受激素和cAMP调节。我们推测，在基质细胞分化的初始阶段，αSMA的表达受基质细胞整合素与分泌的细胞外基质蛋白（ECM）之间相互作用的调节。响应妊娠，由cAMP信号转导介导的滋养层“因子”诱导蜕膜化基质成纤维细胞中IGFBP-1的表达。IGFBP-1的这种诱导与αSMA的消失和新生蛋白质合成相关。我们的比较研究表明，人类和狒狒的蜕膜化过程涉及相似的机制。然而，这两个物种蜕膜化所需的代谢途径对外部刺激的敏感程度似乎有所不同。本综述重点关注可能潜在调节灵长类动物蜕膜化的细胞事件及其在调节滋养层迁移中的作用。
