Extravillous trophoblasts (EVTs) are specialized cells that develop during pregnancy. They play a fundamental role in establishing a healthy pregnancy by integrating the placenta with the mother’s uterus.
The Placenta’s Specialized Cells
Extravillous trophoblasts originate from progenitor cytotrophoblasts within the outer layer of the early embryo’s blastocyst. These cells differentiate and migrate away from the main placental villi, moving into the maternal decidua, the specialized uterine lining prepared for pregnancy.
Upon differentiation, EVTs lose their typical epithelial characteristics and gain the ability to invade tissues, a process linked to epithelial-mesenchymal transition. They are found in specific locations within the uterus, including the decidual stroma and the walls of the maternal spiral arteries. Some EVTs, called interstitial trophoblasts, penetrate the uterine interstitium, while others, known as endovascular trophoblasts, invade the maternal spiral arteries.
Essential Roles in Pregnancy Establishment
Extravillous trophoblasts have several essential functions. One primary role is anchoring the developing placenta securely to the uterine wall. Interstitial trophoblasts invade the decidual stroma, physically connecting the placenta to the mother’s uterus.
Another key function is remodeling the maternal spiral arteries. These narrow, high-resistance vessels are transformed into wide, low-resistance conduits, ensuring adequate blood flow to the growing fetus. Endovascular trophoblasts invade the artery lumen, replacing endothelial cells and disrupting muscular layers. This makes vessels less responsive to maternal vasoconstriction and increases their blood delivery capacity.
During the first trimester, endovascular trophoblasts temporarily plug the maternal spiral arteries, maintaining a low-oxygen environment within the placenta. This initial hypoxia protects the early fetus and placenta from oxidative stress. As the pregnancy progresses, these plugs dissolve, allowing maternal blood perfusion to begin, which supports further fetal and placental development.
Extravillous trophoblasts also contribute to modulating the maternal immune response. The fetus is considered semi-allogeneic, meaning it carries genetic material from both parents, making it somewhat foreign to the mother’s immune system. EVTs interact with maternal immune cells, such as uterine natural killer cells, to promote immune tolerance and prevent the mother’s body from rejecting the developing fetus.
Impact on Pregnancy Health
Properly functioning extravillous trophoblasts are important for a healthy pregnancy outcome. Their actions lay the foundation for adequate fetal growth and well-being. Disruptions in EVT invasion, migration, or remodeling can lead to various pregnancy complications.
One complication is preeclampsia, characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. This disorder is often linked to inadequate spiral artery remodeling, where EVTs fail to transform maternal vessels. This leads to insufficient placental blood flow, impacting both maternal and fetal health.
Fetal growth restriction (FGR), where the fetus does not grow as expected, is also frequently associated with EVT dysfunction. This condition is often a consequence of the inadequate blood supply resulting from compromised spiral artery remodeling. When the placenta cannot receive enough blood, it struggles to deliver sufficient nutrients and oxygen to the fetus, limiting its growth.
Dysfunction of extravillous trophoblasts can also be linked to early pregnancy loss. The initial establishment of pregnancy, including secure placental anchoring and proper vascular remodeling, relies on these cells. Any significant failure in these early processes can lead to pregnancy loss.