Trophoblast lineage-specific differentiation and associated alterations in preeclampsia and fetal growth restriction

Abstract

The human placenta is a poorly-understood organ, but one that is critical for proper development and growth of the fetus in-utero. The epithelial cell type that contributes to primary placental functions is called "trophoblast," including two main subtypes, villous and extravillous trophoblast. Cytotrophoblast and syncytiotrophoblast comprise the villous compartment and contribute to gas and nutrient exchange, while extravillous trophoblast invade and remodel the uterine wall and vessels, in order to supply maternal blood to the growing fetus. Abnormal differentiation of trophoblast contributes to placental dysfunction and is associated with complications of pregnancy, including preeclampsia (PE) and fetal growth restriction (FGR). This review describes what is known about the cellular organization of the placenta during both normal development and in the setting of PE/FGR. It also explains known trophoblast lineagespecific markers and pathways regulating their differentiation, and how these are altered in the setting of PE/FGR, focusing on studies which have used human placental tissues. Finally, it also highlights remaining questions and needed resources to advance this field.

Decreased circUBAP2 Expression Is Associated with Preeclampsia by Limiting Trophoblast Cell Proliferation and Migration

“…A successful pregnancy depends on the proper invasion of trophoblast cells into decidual tissue to promote embryo implantation and the reconstruction of extracellular matrix and blood vessels to maintain normal physiological functions of the placenta [ 20 ]. Abnormal invasion of trophoblast cells may result in too deep or too shallow penetration, which prevents remodeling of the uterine spiral artery, causes anoxia and ischemia of the placenta, and results in damage to endothelial cells of the whole blood vessels of the mother; these changes cause various adverse pregnancy outcomes and pregnancy-related diseases, such as fetal growth restriction, embryo discontinuation, placental abruption, and PE [ 21 , 22 ]. Normal proliferation and differentiation of trophoblasts is a prerequisite for placental formation [ 23 ].…”

Modeling preeclampsia using human induced pluripotent stem cells

“…This constellation of findings is referred to as maternal vascular malperfusion (MVM) and has been associated with PE and/or fetal growth restriction, particularly in severe cases 12 . These histopathologic changes are accompanied by documented abnormalities in CTB, STB, and EVT 13 , as well as molecular evidence of oxidative stress as a result of abnormal maternal vascular remodeling 14 – 16 . The unique nature of these histologic and molecular findings accompanying the clinical disorder in humans has limited the utility of animal models of PE.…”

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

“…One of the major events during the process of placentation is invasion of extravillous trophoblasts (EVT) [1]. Incomplete and shallow invasion can lead to the development of pregnancy disorders, including intrauterine fetal growth restriction (IUGR), preterm labor, miscarriage, and, most commonly, PE [2,3]. There is no consistent and uniform classification of PE, but the one based on the severity of symptoms into mild and severe PE is commonly used [4][5][6].…”