Molecular and cellular underpinnings of normal and abnormal human placental blood flows

Abnormal placental function is well-established as a major cause for poor pregnancy outcome. Placental blood flow within the maternal uteroplacental compartment, the fetoplacental circulation or both is a vital factor in mediating placental function. Impairment in flow in either or both vasculatures is a significant risk factor for adverse pregnancy outcome, potentially impacting maternal well-being, affecting immediate neonatal health and even influencing the long-term health of the infant. Much remains unknown regarding the mechanistic underpinnings of proper placental blood flow. This review highlights the currently recognized molecular and cellular mechanisms in the development of normal uteroplacental and fetoplacental blood flows. Utilizing the entities of preeclampsia and fetal growth restriction as clinical phenotypes that are often evident downstream of abnormal placental blood flow, mechanisms underlying impaired uteroplacental and fetoplacental blood flows are also discussed. Deficiencies in knowledge, which limit the efficacy of clinical care, are also highlighted, underscoring the need for continued research on normal and abnormal placental blood flows.