Angiogenesis in the Placenta: The Role of Reactive Oxygen Species Signaling

Figure 1

Oxidative stress throughout human pregnancy and its relation to placental angiogenesis. At the beginning of the first trimester of pregnancy, there are low levels of systemic oxidative stress and no blood flow into the placenta because extravillous trophoblasts (EVTs) (depicted as light purple circles) plug the maternal spiral arteries (depicted in red) in the decidua as shown in the first panel. Between 8 and 12 weeks of gestation, the EVT plug dissipates and the EVTs invade maternal spiral arteries to allow blood to enter the placenta (black arrow), as illustrated in the second panel. This coincides with a sharp increase in maternal oxidative stress. Furthermore, the state of oxidative stress increases with gestational age as depicted by the black curve. The first signs of placental angiogenesis occur at 3 weeks of gestation. However from about 12 weeks onwards, blood vessels (red lines) protrude towards the trophoblastic layers of the villi (outlined in green), where blood exchange between maternal and fetal circulation is optimal (shown in panel three). From about 9–23 weeks of gestation, there is an expansion of the fetal capillary bed by branching and nonbranching angiogenesis (dashed red lines in angiogenesis panel). From 23-24 weeks of gestation, the greatest changes in blood vessel development and villous composition are observed (peak angiogenesis panel) [22, 34]. Angiogenesis continues until term with the maturation of blood vessels and development of a more complex vascular network to facilitate exponential fetal growth (last panel). The horizontal black arrows indicate the approximate time each process depicted in the panels occurs. Note: this graph has been constructed by interpretations of multiple studies reporting findings of systemic oxidative stress markers present in women during normal pregnancy [35–40] as studies on placental/uterine oxidative stress are limited [32].