Arginine is a common substrate for nitric oxide (NO) and polyamine syntheses via NO synthase (NOS) and ornithine decarboxylase (ODC) (19). NO is a major endothelium-derived relaxing factor, and plays an important role in regulating placental-fetal blood flows and, thus, the transfer of nutrients and O2 from mother to fetus (20). Likewise, polyamines regulate DNA and protein synthesis, and therefore, cell proliferation and differentiation (19,21). Thus, NO and polyamines are key regulators of angiogenesis (the formation of new blood vessels from preexisting vessels) and embryogenesis (22), as well as placental and fetal growth (Fig. 1). These crucial roles of NO and polyamines are graphically illustrated by the following findings. First, inhibition of NO synthesis by NOS inhibitors in rats or the absence of NO synthesis in eNOS-knockout mice results in IUGR (23). Second, inhibition of polyamine synthesis prevents mouse embryogenesis, and inhibition of placental polyamine synthesis reduces placental size and impairs fetal growth (21). Third, IUGR in humans is associated with impaired whole body NO synthesis (24) and with decreases in arginine transport, eNOS activity, and NO synthesis in umbilical vein endothelial cells (25). Finally, maternal arginine deficiency causes IUGR, increases fetal resorption and death, and increases perinatal mortality in rats, whereas dietary arginine supplementation reverses fetal growth restriction in rat models of IUGR induced by hypoxia or inhibitors of NOS