12 Trophoblast Stem Cells

THE TROPHOBLAST LINEAGE AND PLACENTAL DEVELOPMENT In the mammalian embryo, the formation of the extraembryonic lineages, the trophectoderm and primitive endoderm, precedes the differentiation of cells that will contribute to the fetus itself. The precocious differentiation of these lineages in mammals is related to their essential roles in promoting survival of the embryo in the uterine environment. Cells of the primitive endoderm give rise to the endoderm layers of the yolk sacs, whereas descendants of the trophectoderm will form the trophoblast portion of the placenta (Fig. 1). The development of both extraembryonic lineages has been reviewed previously (Rossant 1986Rossant 1995). The scope of the following discussion is to provide an overview of trophectoderm development in the preimplantation embryo and of the trophoblast lineage and placenta in postimplantation stages, as the basis for the study of trophoblast stem cells. The trophectoderm is the first cell type to differentiate in the mammalian embryo. In the mouse, it is morphologically distinguishable by the blastocyst stage (3.5 days post coitum [dpc]), where it forms an outer monolayer of cells surrounding the blastocoelic cavity and the inner cell mass (ICM) (Fig. 1A). The trophectoderm cells are characterized by their flattened epitheloid-like appearance, with apical tight junction complexes. In addition, trophectoderm cells harbor sodium pumps (Na + , K + -ATPase) whose activity leads to accumulation of fluid within the blastocoel cavity, resulting in blastocoel expansion. This process is thought to facilitate hatching from the zona pellucida, a thick protein coat surrounding the embryo (Wiley et al. 1990). The distinction...