The placenta is essential to a healthy start in life, carrying out the work of several organs while they’re still being formed. If underdeveloped, it can cause complications that impact the fetus and lead to long-term health issues, including fetal growth restriction — a condition associated with brain and heart diseases — preterm births, and miscarriages. But, despite the importance of the placenta in the health of all children, little is known about it, including why it might not develop properly.
“My team is working to understand the specific process behind placenta development, the intrinsic defects that may affect it, and how these defects translate into disorders such as fetal growth restriction,” says Dr. Alexander Beristain, investigator at BC Children’s Hospital Research Institute (BCCHR) and Associate Professor in the Department of Obstetrics and Gynaecology at the University of British Columbia (UBC).
In a paper recently published in Developmental Cell, Dr. Beristain’s team investigated two state-of-the-art stem cell-based tools that model a human placenta in the first trimester of a pregnancy. “The first three months are key for the health of the fetus, but we don’t know much about what the cells are doing and the role they play,” Dr. Beristain says. Considering the importance of genetics in the studies conducted by his lab, his team has been working closely with Dr. Wendy Robinson, Associate Director and investigator at BCCHR, and Professor in the Department of Medical Genetics at UBC.
SIGNIFICANT ROLE
The placenta starts developing inside the uterus on day zero of a pregnancy, and is delivered in the last stage of labour (or removed, in the event of a C-section). This temporary organ should be fully developed by week 10, and it only expands to accommodate the growing fetus.
Rich in blood vessels, the placenta plays a significant role in keeping the fetus alive and healthy. Through the umbilical cord, it supplies the fetus with oxygen, nutrients, and antibodies, and removes carbon dioxide and waste products from their blood.
Some complications such as preeclampsia — a high blood pressure disorder that can occur during a pregnancy — affect the blood supply to the placenta. If there’s insufficient amount of blood, the fetus may not receive enough oxygen and nutrients, which can lead to fetal growth restriction, an indication that they haven’t reached their growth potential.
CULTURE SYSTEMS
Complications could be prevented if we knew more about how the placenta develops and interacts with the uterus. Fortunately, newly developed lab-based systems are making it easier to study the formation of the placenta and the development of trophoblasts — the cells that provide nutrition to the fetus. By producing mini placentas cultured in the lab, the researchers aim to understand the specific environmental factors in the uterus, how primitive cells develop into this organ, and the critical processes controlling these cells.
“It’s important to understand how the placenta interacts with a person’s immune system and protects the fetus from stressors like infections and harmful substances,” says Dr. Beristain. Culture systems can provide insights on aspects of the placenta that contribute to disorders, including deficiencies and genetic mutations.
“Once we know what happens, we can look for ways to either identify when things are going wrong earlier or help improve placenta development.”
Knowledge of human stem cell development has led to better models for studying the placenta, facilitating more accurate models of trophoblast development. “We have been able to make these models so that at a molecular level they match quite closely to the placenta in pregnancy, replicating what happens in the human body,” Dr. Beristain says.
Reliable models are crucial because, for this type of study, researchers can’t use the placenta of humans or other species. In humans, in-depth research would require samples of the placenta during pregnancy for biopsy. But the collection of these samples would be too invasive and risky for the fetus. As for other species, even though most mammals have a placenta, the organization and the specific types of placenta cells are quite different from humans.
“With the more reliable human-based models available nowadays, researchers can better understand the placenta,” says Dr. Beristain.
There’s a thirst for knowledge. The placenta is understudied mainly due to limited models of this organ and limited funds for women’s health research — a situation that impacts any person with a uterus. It was only in 2018 that, for the first time, stem cells from this organ were isolated. That was notable because conducting research on isolated cells allows scientists to answer specific research questions with less interference from other cell types in the sample.
Dr. Beristain has a background in stem cell biology and mammary gland development. His primary research focus is immunology and placental biology, and he’s been involved with placental research since the 2000s. With his current study, Dr. Beristain hopes to find answers that can positively impact the health of children. “With accurate tools and models, we can now aim to understand the step-by-step processes that make a healthy placenta, but also what processes contribute to a poorly developed one,” he says. “There is also the potential in the future to find ways to intervene and prevent the complications of an underdeveloped placenta, allowing more children to enjoy the best possible start in life.”
