NADPH oxidase as an important source of reactive oxygen species at the mouse maternal–fetal interface: putative biological roles

Oxygen derivatives that comprise the large family of reactive oxygen species (ROS) are actively involved in placental biology. They are generated at the maternal–fetal interface at the level of decidual, trophoblast and mesenchymal components. In normal conditions, ROS produced in low concentrations participate in different functions as signalling molecules, regulating activation of redox-sensitive transcription factors and protein kinases involved in cell survival, proliferation and apoptosis, hence much of cell functioning. Physiological ROS generation is also associated with such defence mechanisms as phagocytosis and microbiocidal activities. In mice, particularly but not exclusively, trophoblast cells phagocytose intensively during implantation and post-implantation periods and express enzymic machinery to address a ROS-producing response to changes in the environment. The cells directly associated with ROS production are trophoblast giant cells, which mediate each and every relationship with the maternal organism. In this review, the production of ROS by the implanting mouse trophoblast is discussed, focusing on NADPH oxidase expression, regulatory mechanisms and similarities with NOX2 from phagocytes. Some of the current controversies are assessed by attempting to integrate data from studies in human trophoblast and mouse models.Although oxygen is vital for life, in specific conditions it can also give rise to unstable molecules, the reactive oxygen species (ROS). In physiological conditions, ROS are used as a defence mechanism by immune cells and as messengers for cell survival, proliferation and death among neighbouring cells. However, due to their high capability to react with other organic molecules changing their structure and function, such as proteins, lipids and DNA, ROS can also cause biological damage, which in general occurs when natural antioxidant mechanisms are unable to counterbalance the reactivity of these molecules. NAD(P)H oxidase is an enzymic complex able to generate a large amount of ROS. Production of ROS has been described at the maternal–fetal interface in many species and is associated with an unbalance and gestational diseases such as pre-eclampsia and hypertension. This review discusses the physiological NADPH oxidase expression by the fetal component of the mouse placenta, the trophoblast, which mediates each and every relationship with the maternal organism.