School of Medicine


Trophoblast deportation and effects on the maternal immune and vascular systems

The human placenta is bathed in maternal blood and as cells on the surface of the placenta grow old and die they are shed into the maternal blood either as very large multinucleated structures called syncytial knots or as mononuclear cytotrophoblasts. These shed cells are then deported in the maternal blood and become lodged in the capillaries of the maternal lungs.

We are studying the mechanisms by which syncytial knots and other trophoblast debris is removed from the maternal lungs. We have shown that both immune cells and the endothelial cells that line blood vessels can phagocytose (eat) the dead syncytial knots. Importantly, the manner in which syncytial knots died greatly influences the responses of the phagocytosing cells. If the syncytial knots die by apoptosis – controlled cell death (suicide), then they are phagocytosed “silently”. However, if the syncytial knots die by necrosis (pathological cell death), then phagocytosing endothelial cells become activated. Endothelial cell activation is a characteristic feature of the pregnancy disease pre-eclampsia and we are investigating whether syncytial knots contribute to the pathogenesis of pre-eclampsia. One of the major advances we have made in this area is to develop an in-vitro model that allows us to harvest substantial numbers of syncytial knots so that we can study their effects on other cells (Abumaree et al. 2006).

syncytialknotbeads
A syncytial knot with its many nuclei stained dark blue was harvested using magnetic beads (small orange circles).

Current investigations include:

  1. Once activated do endothelial cells secrete factors that induce activation of further endothelial cells?
  2. What factors influence the nature of cell death for syncytial knots?
  3. Do apoptotic syncytial knots produce immunosuppressive responses in leukocytes?
  4. What are the physical processes that lead to syncytial knot shedding?
  5. What is the distribution of syncytial knots in the maternal body?
  6. In collaboration with Associate Professor S Malpas (Dept Physiology) and Dr Sarah-Jane Guild (Dept Physiology) we are investigating whether necrotic syncytial knots can induce blood pressure changes since increased blood pressure is the major maternal symptom of preeclampsia.

Funding for this work was provided by:

  • Marsden Fund of the New Zealand Royal Society
  • The Auckland Medical Research Foundation
  • The New Zealand Lotteries Board (Health)
  • The University of Auckland Staff Research Fund
  • The Auckland Medical Aid Trust
  • The Maurice and Phyllis Paykel Trust.