Blastocyst invasion and the stromal response in primates

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.