A University of Alberta research team has identified a protein that is key to the formation of a healthy placenta during pregnancy.
The placenta is the organ that surrounds and protects the fetus, letting oxygen, nutrients and hormones pass safely from the mother to the growing baby.
The team used in vitro tests on human placental cells and also created organoids — mini-placentas in a dish that self-assemble from placental stem cells.
They studied the trophoblasts, cells that form the outer surface of the placenta. These cells start out as single cells with instructions from a protein called YAP1 to simply multiply.
The research team isolated the specific protein, called aPKC-ζ III, that then switches off YAP1, causing the cells to fuse together and form a giant outer protective layer known as the syncytiotrophoblast.
The discovery provides insight into why placental formation can be disrupted during pregnancy by stressors such as inflammation and low oxygen, potentially leading to serious disorders such as preeclampsia, which can harm both mother and baby.
It also opens up new avenues for targeted therapeutic interventions to fine-tune the cell signalling mechanisms.
“This paper underscores how using in vitro models can lead us to uncover overlooked or altered signalling pathways that are important for human biology, but may not even be present in other species,” says principal investigator Meghan Riddell, associate professor of obstetrics and gynecology. “It’s a really good example of the benefits of doing tissue-specific and pregnancy-specific research.”
The Riddell lab also studies the molecular mechanisms controlling the growth of blood vessels, or angiogenesis, at the interface between the placenta and mother, and how it can be disrupted by pregnancy complications.
The work was supported through the Natural Sciences and Engineering Research Council of Canada; the Women and Children’s Health Research Institute and their donors the Alberta Women’s Health Foundation and the Stollery Children’s Hospital Foundation; the Canada Research Chairs program; and the Canada First Research Excellence Fund.