Low Oxygen Enhances Trophoblast Column Growth by Potentiating Differentiation of the Extravillous Lineage and Promoting LOX Activity
This week we profile a recent publication in Development from Jenna Treissman (pictured) in
the laboratory of Dr. Alexander Beristain at the BC Children’s Hospital Research Institute.
Can you provide a brief overview of your lab’s current research focus?
The Beristain lab’s primary focus is aimed at generating knowledge to help better understand early developmental events that take place in pregnancy and that ultimately impact the health of the mother and developing baby. To this end, we have two major research arms: One dedicated to understanding cellular processes important in placental development, and the other focused on understanding how the mother’s immune system communicates with the baby and the placenta. Over the last two to three years, new technologies such as single cell transcriptomics, regenerative three-dimensional culture systems, and stem cells have been embraced by our lab to tackle important questions related to human placental development. Surprisingly, very little is known about the placenta, likely because historically little importance has been placed on this temporary organ. However, this is rapidly changing as scientists and clinicians are beginning to appreciate that what goes on during pregnancy with regards to placental and fetal health has both immediate and long-lasting consequences to an individual’s health.
What is the significance of the findings in this publication?
Understanding how the placenta regulates delivery of maternal oxygen and nutrients to the baby is very important because many pregnancy disorders are associated with insufficient placental development or reduced access to maternal blood. One important process that takes place around four to six weeks of gestation in humans is the transition of specialized placental cells, called trophoblasts, into highly invasive cell types that invade into the mother’s uterus. This process begins before maternal blood supply to the placenta is established and thus occurs in a relatively low oxygen environment. Oxygen sensing mechanisms in cells control processes such as cell lineage commitment, proliferation, survival and others, but the role of low oxygen in early placental development is controversial and inconclusive. Our research tackles this problem by integrating advanced placental cell cultures exposed to low, moderate and high levels of oxygen with non-biased conventional transcriptomic and single-cell transcriptomic approaches. Our data shows that exposure to low oxygen conditions promotes the differentiation of primitive trophoblasts toward advanced invasive cell types, while culture in high oxygen conditions slows this process. These findings are important because they identify several molecular processes regulated by low oxygen conditions that are critical to the early stages of healthy placental development.
What are the next steps for this research?
A result of this research is that we have identified a number of candidate molecular processes potentially important in early placental development. Our next steps will aim to test the importance of these pathways using state-of-the-art human trophoblast stem cell and regenerative 3D culture systems to determine their importance in early placental development and long-term health. These findings may shed light on how adverse placental development occurs in the context of high-risk pregnancies.
This work was funded by:
This research was funded by a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant, and a Canadian Institutes of Health Research (CIHR) Project Grant. Jenna Treissman was supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship.