Syncytial Knots, Sprouts, Apoptosis, and Trophoblast Deportation from the Human Placenta

SummaryThe syncytiotrophoblast (STB) that forms the epithelial covering of the placental villous tree has a unique cell biology on account of its syncytial nature. The tissue is in a terminally-differentiated, postmitotic state, and expands through the recruitment by fusion of underlying progenitor cytotrophoblast cells. This process occurs from the time of implantation until term, and so its nuclei will be of various ages, producing a spectrum of contrasting appearances; whilst some are euchromatic, others display dense condensations of heterochromatin, the latter often aggregating to form clusters referred to as syncytial knots. These appearances have led to the suggestion that knots are apoptotic, and a hypothesis has developed that the nuclei are transcriptionally inactive and transit through the STB before being shed into the maternal circulation. Here, we review the evidence for this hypothesis, looking at the morphology of the nuclei, their number throughout gestation, evidence of transcriptional activity, and trophoblast deportation. We conclude that there is little evidence to support the concept that turnover of syncytial nuclei takes place in the normal placenta, or that this occurs through an apoptotic-related process. Instead, we suggest that a proportion of syncytial nuclei are transcriptionally active, that epigenetic modifications underlie the changes in chromatin appearance, and that syncytial nuclei continue to accumulate until term. We recognize that apoptotic changes can occur in pathologic pregnancies, but consider the deportation of trophoblast that has been linked to preeclampsia to be most likely of necrotic origin following ischemic injury.