Regulation of the brain-placental axis, and its relevance to the health and disease of the offspring.

The placenta develops as a transient organ during pregnancy to nurture the growing fetus. It supplies nutrients and oxygen to the fetus, collects fetal waste, and safeguards the fetus from infections and adverse pregnancy conditions. Emerging evidence suggests that the placenta plays adaptive functions to protect the developing brain from injury in adverse maternal conditions. Inadequate placental support can impact the developmental process of the brain, which increases the risk of brain diseases among the offspring. There is a remarkable coordination in gene expression between the placenta and fetal brain of mice, suggesting a robust regulation of the brain-placental axis. The deregulation of the brain-placental axis can have adverse effects on the fetal programming of brain development. Defective neuronal development of the fetus due to the abnormal or non-optimal placental functions can lead to an increased risk of different neuropsychiatric diseases in the adult life of the offspring. Thus, there is a growing interest to understand placental influences on fetal brain development and its links to the risk of brain diseases. Research on the brain-placental axis, also referred to as neuroplacentology, is a rapidly emerging interdisciplinary field that integrates concepts and tools from diverse areas, including reproductive biology, neuroscience, epigenetics, systems biology, and data sciences, among others. Recently, large-scale multiomics data and systems biology approaches have been applied to investigate the functional links between the placenta and fetal brain, and to dissect the cellular and molecular mechanisms of the regulation of the brain-placental axis. The primary objective of this review is to outline the current status and the future avenues of this emerging research field that holds huge potential to advance our knowledge about the role of the placenta in the developmental origin of brain health and disease.