Figure 1

Redox-regulated signaling in normal pregnancies and in Comt-deficient mutant mice. A, Shows that ROS-induced signaling (Lo ROS) is essential for implantation, establishment and maintenance of pregnancy. The absence of ROS (No ROS) or its excessive accumulation (Hi ROS) are detrimental to pregnancy; B, in Comt^+/+ mice (WT), 2ME2 production is highest at late pregnancy and blocks vascular growth by destabilizing HIF-1α in physiological pregnancies. The absence of 2ME2 in Comt^-/- animals (mutant) would increase oxidative stress and stabilize HIF-1α. The stability of HIF-1α is dependent upon critical concentration of H₂O₂ which determines the functional state of prolyl hydroxylases (PHD).