The significance of elevated placental PHLDA2 in human growth restricted pregnancies

In utero growth restriction is the failure of a fetus to achieve its genetic growth potential during gestation. Elevated expression of the maternally expressed imprinted gene PHLDA2, has been reported in the human placenta of growth restricted pregnancies. A mouse modelling this alteration has been generated and also displays fetal growth restriction suggesting that increased expression of PHLDA2 is not an effect but rather a cause of growth restriction in human pregnancies. Here we review the current data linking PHLDA2 to growth restriction and the data from human and animal model studies suggesting that placental PHLDA2 expression may be responsive to environmental stimuli such as maternal lifestyle. Further investigation is warranted in larger studies of human placentas with the aim of determining whether placental PHLDA2 expression could be used as a diagnostic tool to identify or sub-classify growth restricted infants and to inform more effective interventions and treatment for IUGR in the future.