Functional regulation of human trophoblast differentiation

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

“…Although there was a normal syncytialization response to EGF, it is known that syncytialization, which includes cell fusion to form giant cells (syncytia) as well as numerous biochemical changes, is regulated by a large variety of factors that might be abnormal in PE. 21,42 For example, syncytin, an inducer of cell membrane fusion, is reduced in PE. 43 The data also show that despite a normal syncytia formation response to EGF, the syncytia thus formed were abnormal and unable to secrete normal amounts of ADM, as would be expected of normal control cells (Figure 2).…”

“…It is known that multiple cytokines regulate placental function 21 and that many cytokine abnor-malities exist in PE, 7 including elevated serum tumor necrosis factor-␣ (TNF-␣). 22 Other studies have demonstrated that TNF-␣ and interferon-␥ (IFN-␥) induce trophoblast apoptosis and that this effect is blocked by epidermal growth factor (EGF).…”

Activin/Nodal Signaling Switches the Terminal Fate of Human Embryonic Stem Cell-derived Trophoblasts

“…Treatment with bone morphogenetic protein (BMP) and/or inhibitors of the activin/nodal pathway have been used for deriving trophoblasts (1, 6 -8, 10, 12-15, 17, 19, 22-29, 33, 38). However, the signaling pathways that guide terminal trophoblast differentiation toward a syncytial fate versus an extravillous fate are poorly understood (39). Trophoblasts of the human placenta are composed of villous cytotrophoblasts (vCTBs), syncytiotrophoblasts (STBs), and extravillous cytotrophoblasts (EVTs) (40).…”

Expression of genes, encoding the enzymes of cysteine metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy

“…Human placentas in the first and third trimesters significantly differ in their structure and weight; in anaerobic and aerobic metabolism; histiotrophic and hemotrophic nutrition; invasive and syncytial phenotype, as well as in alterations of gene expression profiles [11,27,32,33]. We suggested that the transition from histiotrophic nutrition in the first trimester to hemotrophic nutrition in the second and third trimesters is accompanied by a greater cysteine supply to placenta and activation of cdo expression via yet unknown mechanism.…”