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How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation

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Abstract

In humans, cell fusion is restricted to only a few cell types under normal conditions. In the placenta, cell fusion is a critical process for generating syncytiotrophoblast: the giant multinucleated trophoblast lineage containing billions of nuclei within an interconnected cytoplasm that forms the primary interface separating maternal blood from fetal tissue. The unique morphology of syncytiotrophoblast ensures that nutrients and gases can be efficiently transferred between maternal and fetal tissue while simultaneously restricting entry of potentially damaging substances and maternal immune cells through intercellular junctions. To maintain integrity of the syncytiotrophoblast layer, underlying cytotrophoblast progenitor cells terminate their capability for self-renewal, upregulate expression of genes needed for differentiation, and then fuse into the overlying syncytium. These processes are disrupted in a variety of obstetric complications, underscoring the importance of proper syncytiotrophoblast formation for pregnancy health. Herein, an overview of key mechanisms underlying human trophoblast fusion and syncytiotrophoblast development is discussed.

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Acknowledgements

The authors would like to thank Tunyalux Langsub for illustrative assistance.

Funding

This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC 5053, to SJR). MJJ was supported by an Alexander Graham Bell Canada Graduate Scholarship.

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  1. Department of Anatomy and Cell Biology and Children’s Health Research Institute, University of Western Ontario, London, ON, N6A5C1, Canada

    Stephen J. Renaud & Mariyan J. Jeyarajah

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Renaud, S.J., Jeyarajah, M.J. How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation. Cell. Mol. Life Sci. 79, 433 (2022). https://doi.org/10.1007/s00018-022-04475-z

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