Scientists have made headway in understanding how pathogens, such as the Zika virus, cross from the mother to the unborn child and cause birth defects, according to research published in Science Advances.
Before a child is born, it is the placenta that anchors him or her to the uterus, providing nourishment and preventing the transfer of microorganisms from an infected mother.
However, the placenta is a complex and poorly understood organ.
Research so far has involved obtaining and studying placental cell lines. However, these cells do not fuse spontaneously to form the type of structure that is characteristic of the human placenta.
Another strategy has been to isolate cells called primary human trophoblasts from the placenta after childbirth, but such cells are hard to obtain, and they do not divide.
They are also more difficult to manipulate genetically, and this hinders progress in learning about biochemical pathways that have a role in placental function.
Researchers – led by Carolyn Coyne, PhD, associate professor of microbiology and molecular genetics at the Pitt School of Medicine at the University of Pittsburgh in Pennsylvania, and a member of the Magee Women’s Research Institute (MWRI), also in Pittsburgh – have now devised a cell-based model that could shed new light on how the placenta works.
- Placental problems are more likely in mothers aged over 40 years
- The placenta is normally delivered around 5 minutes after the birth
- Substances that cross the placental barrier include alcohol, caffeine, cocaine and tobacco.
Coyne’s team cultured a human placental trophoblast cell line using a microgravity bioreactor system that was developed by the National Aeronautics and Space Administration (NASA).
These trophoblasts were added to small dextran beads with blood vessel cells and spun in a container filled with cell culture fluid.
The resulting shear stress and rotational forces created an environment similar to that found at the maternal-fetal interface, achieving something that static cell-culture systems had not been able to do. The cells fused to form syncytiotrophoblasts that resembled the primary cells that line the outermost layer of the human placental tissue.
Next, the researchers tested the functional properties of the model.
They exposed the model to a virus and to Toxoplasma gondii, a parasite found in cat feces. T. gondii is known to cause fetal infection, resulting in miscarriage, congenital disease and/or disability.
The syncytiotrophoblasts successfully resisted infection by the virus and by three different strains of the parasite, having formed a barrier in the same way as naturally occurring cells do.
In future, the authors hope that experimentation with the model will help to uncover which biological factors would allow an infectious agent to pass through the placental barrier to the unborn child.
Tests on the effects of the Zika virus and other pathogens linked to congenital disease have already begun.
“The human placenta is unique and unlike that of other many other placental mammals. With our new model in the research toolkit, we and other scientists hope to advance our knowledge of the placenta, examine its function and learn how it can prevent most, but not all, maternal infections from causing problems for the baby.