Sphingolipid biosynthesis, metabolism and actions in placental trophoblast differentiation

[Truncated abstract] Formation and maintenance of the syncytiotrophoblast layer of the human placenta involves the fusion and terminal differentiation of trophoblast cells, the specialized cell type of the placenta. This process is unique and although it has been actively investigated over recent years, it remains incompletely understood. Sphingolipids such as sphingosine and ceramide are important endogenous cellular components which are controlled at the level of synthesis, metabolism and distribution, and act as regulators of numerous cellular functions including apoptosis and differentiation. The role of sphingolipids in trophoblast apoptosis, differentiation and fusion has not been elucidated in detail, apart from a study by Johnstone et al. indicating a negative role of sphingosine-1-phosphate (S1P) in this process. A previous work from our laboratory also implicated a role for ceramide in this process. The aim of this project, therefore, was to examine the production, metabolism and actions of key sphingolipids - ceramide, sphingosine and S1P - during spontaneous trophoblast differentiation in vitro to determine their role(s) in the differentiation process.