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Mechanistic insights into the development of severe fetal growth restriction

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CLINICAL SCIENCE
卷 137, 期 8, 页码 679-695

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PORTLAND PRESS LTD
DOI: 10.1042/CS20220284

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Fetal growth restriction (FGR) caused by suboptimal placental function leads to significant risks for adverse outcomes in both the short and long term. Delivery is currently the only treatment available, but it does not improve outcomes for survivors. The long-term consequences of FGR can lead to a multi-generational cascade of adverse effects. Understanding the mechanisms of placental-mediated FGR is crucial for improving outcomes and overall health.
Fetal growth restriction (FGR), which most commonly results from suboptimal placental function, substantially increases risks for adverse perinatal and long-term outcomes. The only treatment that exists is delivery, which averts stillbirth but does not improve out-comes in survivors. Furthermore, the potential long-term consequences of FGR to the fe-tus, including cardiometabolic disorders, predispose these individuals to developing FGR in their future pregnancies. This creates a multi-generational cascade of adverse effects stem-ming from a single dysfunctional placenta, and understanding the mechanisms underlying placental-mediated FGR is critically important if we are to improve outcomes and overall health. The mechanisms behind FGR remain unknown. However, placental insufficiency de-rived from maldevelopment of the placental vascular systems is the most common etiology. To highlight important mechanistic interactions within the placenta, we focus on placental vascular development in the setting of FGR. We delve into fetoplacental angiogenesis, a robust and ongoing process in normal pregnancies that is impaired in severe FGR. We re-view cellular models of FGR, with special attention to fetoplacental angiogenesis, and we highlight novel integrin-extracellular matrix interactions that regulate placental angiogenesis in severe FGR. In total, this review focuses on key developmental processes, with specific focus on the human placenta, an underexplored area of research.

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