Developmental cell biology of human villous trophoblast: current research problems

Abstract

The common gestational pathologies are placental and developmental in origin. However, much remains to be learned about the key events of morphogenesis and growth in the placenta. Metabolic settings established early in both the fetus and placenta define their capacity to respond to later challenges, as well as the quality of the response. Placental growth is exponential in the first trimester and involves coordinated events in trophoblast and mesenchyme, with early cell segregation events having a strong influence on growth potential. One of these is the differentiation of progenitor cytotrophoblasts into villous intermediate cells programmed to fuse with the syncytium, or, alternatively, into extravillous migratory cells that transform the maternal vascular supply. In the latter case, contact with decidual extracellular matrix stimulates differentiation, and therefore this decision is influenced by the number of contact sites at the placental periphery, which in turn is a function of branching in the villous tree. The villous trophoblast bilayer is the primary barrier between maternal and fetal tissues. The maternal-facing layer is syncytial and post-mitotic: this limits traffic of pathogens to the fetus and chimaerism arising by shedding of (non-proliferative) syncytial elements into maternal circulation. Conventional cell culture models fail to replicate this critical vectorial relationship. Tissue explants can overcome the problem to some extent, and have been used to show that turnover of trophoblast in the villous environment is regulated by signals from both fetal and maternal tissues. Maternally delivered insulin-like growth factors stimulate growth and might be therapeutically useful when endogenous growth pathways falter.

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

“…These IVT are programmed to either fuse with the syncytium, or are transferred to extravillous trophoblast cells [32]. We found a downregulation of PPAR in the IVT compartment in both spontaneous and recurrent miscarriage on protein as well as on mRNA-level.…”

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

“…Digestion solutions containing either CCTs or vCTBs were each layered on top of a Percoll gradient [10-70% (vol/vol)] and cells between 35 and 50% of the Percoll layer were collected. Contaminating RBCs were removed by incubating cells with erythrocyte lysis buffer (155 mM NH 4 Cl, 10 mM KHCO 3 , 0.1 mM EDTA, pH 7.3) for 5 min at room temperature and subsequently washed with 1× HBSS. Contaminating stromal cells were depleted from CCT preparations as mentioned above.…”

“…Floating villi, which are bathed in maternal blood after establishment of the fetal-maternal circulation, are necessary for hormone production and nutrient and oxygen transport to the developing fetus (3). The outermost epithelial surface of these villi, the multinuclear syncytium, also termed syncytiotrophoblast (STB), is generated by cell fusion of underlying CTB progenitors (4). On the other hand, anchoring villi attached to the decidua form proliferative cell columns giving rise to differentiated, extravillous trophoblasts (EVTs).…”

Cell specific patterns of methylation in the human placenta

“…29 Defective epigenetic regulation affecting the differentiation of these different cell types may be a unifying mechanism that could illuminate currently unresolved questions about placental development. 30 The normal function of these tissues likely depends not only on the correct epigenetic profiles but also the normal proportion of the different cell types carrying each profile. Variations in the cell-specific profiles or the proportions of specific cell types among samples of the same tissue could result in abnormal development and/or function of this tissue.…”