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Early placental development is characterised by rapid cell differentiation and migration, matrix remodelling and angiogenesis. The enzyme NAD(P)H oxidase is a major source of superoxide anions implicated in signalling pathways regulating these processes in other systems. It is also thought to be involved in oxygen sensing and regulation of the expression of antioxidant genes. We therefore investigated NAD(P)H oxidase activity in placental tissues in early pregnancy and at term, and correlated this with antioxidant capacity. We collected placental tissues from women undergoing termination of pregnancy (n =19; gestational age 11+6 ±1+0 weeks), and those with elective caesarean section at term after uncomplicated pregnancy (n =15; gestational age 38+6 ±0+4 weeks). Tissues were assayed for superoxide production, using lucigenin chemiluminescence, and three independent markers of antioxidant capacity. In human placentas from normal deliveries at term substantial basal NAD(P)H activity was present. Activity was almost threefold higher in early pregnancy (P <0.0001). This was paralleled by higher total antioxidant capacity (P <0.0001), tissue glutathione concentrations (P <0.01) and gluthathione S-transferase enzyme activity (P <0.05) when compared to corresponding term placental values. NAD(P)H oxidase mediated superoxide generation could be an important modulator of the antioxidant defence response in early pregnancy. [Copyright &y& Elsevier]