Fusion of Cytothrophoblast with Syncytiotrophoblast in the Human Placenta: Factors Involved in Syncytialization

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2008; 5 (2): 76-82

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Keywords: Synzytiotrophoblast,  Zytotrophoblast,  cytotrophoblast,  syncytiotrophoblast

Human placental villi are covered by a characteristic epithelial-like layer. It consists of mononucleated cytotrophoblasts and an overlyingsyncytiotrophoblast layer both in contact to the trophoblastic basement membrane. The syncytiotrophoblast mostly lacks DNA replication andseems to transcribe only barely mRNA. Therefore, the syncytiotrophoblast depends on cell compounds delivered by fusing cytotrophoblasts. Delivery of fresh cytoplasmic contents into the syncytiotrophoblast is achieved by continuous fusion with cytotrophoblasts throughout gesta-tion. Fusion between cytotrophoblasts and the syncytiotrophoblast is driven by multiple factors, including environmental growth factors andcytokines, which turn on a specific cascade of fusogenic proteins in cytotrophoblasts destined for fusion. The cascade includes protein kinasesand transcription factors, as well as induced expression of fusion-promoting proteins associated with the cell membrane. Additionally, specificproteases are activated, which cleave and remodel structural proteins to prepare the cell for fusion. However, not only fusogenic proteins, butalso plasma membrane architecture and physicochemical factors such as calcium and oxygen affect intertrophoblastic fusion. Coordinatedaction of all factors involved is crucial for proper cytotrophoblast – syncytiotrophoblast fusion. Deregulation of a single factor might cause aninadequate fusion rate and could lead to pregnancy complications such as preeclampsia or even spontaneous abortion.