Tracking placental development in health and disease

Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal–placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta–blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective. Pre-eclampsia and fetal growth restriction are diseases of pregnancy that arise from disorders of placental development. This Review discusses healthy development of the placenta and considers disease mechanisms, biomarkers and diagnosis of pre-eclampsia and fetal growth restriction. Key points In the first trimester, uterine secretions support embryonic development; remodelling of the maternal vascular supply to the placental site enables increased volume supply of substrates at low pressure as fetal demand increases. Placental growth and branching of the villous tree yield an increasing surface area for substrate transport, which is coordinated with the elaboration of a fetoplacental vascular network. Fetal growth restriction arises when the supply of nutrients and oxygen to the fetus is insufficient because of maternal vascular malperfusion and/or inefficient extraction of substrates by the placenta. Pre-eclampsia is caused by reaction of the placenta to stress, which triggers the release of factors that induce systemic vascular pathology or suppresses factors th