Fetal growth restriction (FGR) most commonly arises due to placental dysfunction, substantially increasing the risk of perinatal and long-term health problems for the offspring. Inadequate angiogenesis is a key hallmark of severe FGR due to defects in endothelial cells and the surrounding extracellular matrix. Now, Emily Su and colleagues find that integrin dysregulation contributes to the reduced angiogenic potential of FGR cells. They discover that fetoplacental endothelial cells derived from FGR pregnancies have reduced migratory capacity, even when plated on exogenous fibronectin. To further dissect the endothelial defects, the authors apply antibodies to block integrin-fibronectin interactions. They observe that control endothelial cells migrate more slowly, whereas the addition of antibodies against αvβ3 did not alter the migration of FGR cells. Although overall levels of integrins are normal in FGR cells, the authors identify significantly more integrins in focal adhesions, which in turn display defects in maturation and turnover. They hypothesise that reduced membrane trafficking, confirmed by a reduction in the number of early and late endosomes, leads to reduced focal adhesion dynamics. Together, these data begin to elucidate a molecular mechanism to explain the reduced angiogenesis observed in severe FGR pregnancies, which may help identify better treatment options in FGR pregnancies.
