Materno-fetal iron transfer and the emerging role of ferroptosis pathways

A successful pregnancy and the birth of a healthy baby depend to a great extent on the controlled supply of essential nutrients via the placenta. Iron is essential for mitochondrial energy supply and oxygen distribution via the blood. However, its high reactivity requires tightly regulated transport processes. Disturbances of maternal-fetal iron transfer during pregnancy can aggravate or lead to severe pathological consequences for the mother and the fetus with lifelong effects. Furthermore, high intracellular iron levels due to disturbed gestational iron homeostasis have recently been associated with the non-apoptotic cell death pathway called ferroptosis. Therefore, the investigation of transplacental iron transport mechanisms, their physiological regulation and potential risks are of high clinical importance. The present review summarizes the current knowledge on principles and regulatory mechanisms underlying materno-fetal iron transport and gives insight into common pregnancy conditions in which iron homeostasis is disturbed. Moreover, the significance of the newly emerging ferroptosis pathway and its impact on the regulation of placental iron homeostasis, oxidative stress and gestational diseases will be discussed.