Endocrine Abstracts

Trophoblasts are the cell type specific to the placenta. The terminally-differentiated multinucleate form, syncytiotrophoblast, covers the surface of placental chorionic villi, forming a large microvillous epithelium in contact with the maternal circulation. This syncytiotrophoblast layer is both the endocrine tissue of the placenta and the site of other placental functions (e.g. gas exchange, transport activities) upon which fetal viability depends. Syncytiotrophoblast cannot regenerate itself, but relies upon continuous fusion with the underlying proliferating villous cytotrophoblasts for growth and renewal.

Since the differentiation stages leading to syncytial fusion activate the same molecular pathway as the initiation stages of apoptosis, syncytialisation is thought to involve the apoptotic cascade. It commences with the activation of initiator caspases such as caspase 8 in the villous cytotrophoblast, resulting in fodrin cleavage and externalization of phosphatidylserine, plasma membrane changes necessary for fusion to occur. Fusogenic proteins such as the captive retroviral protein, syncytin, then promote fusion directly, forming syncytium. The initial apoptotic steps may progress in the syncytiotrophoblast with the activation of effector caspase 3, or by caspase-independent mechanisms such as calpain. However, fulfilment of the apoptotic cascade may be interrupted when syncytial ATP is depleted. Oxidative stress-induced damage to placental mitochondria, as occurs in pregnancy complications e.g. pre-eclampsia, can lead to syncytiotrophoblast degeneration by necrosis. This damage can be ameliorated by anti-oxidant vitamins C and E. Cytotrophoblast fusion into syncytiotrophoblast is balanced by the extrusion of syncytial material (syncytiotrophoblast microparticles (STBM), fetal DNA and RNA) into maternal blood. Like other microparticles, STBM may carry an array of cytokines and membrane-associated agents capable of perturbing leucocytes and endothelium. A consequence of the shed syncytial debris is thus the inflammation of the maternal vascular compartment characteristic of normal pregnancy.