Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas of severely pre-eclamptic patients

Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme of the kynurenine pathway that degrades L-tryptophan, but a wider range of functions have now been proposed for this enzyme, including antioxidant activity. Our previous study revealed that reduced IDO expression in the placenta induces defective feto-maternal immuno-tolerance leading to the onset of pre-eclampsia. In our present study, we assessed the effects of low placental IDO activity as an antioxidant. The placental levels of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a maker for oxidative damage to DNA, were significantly higher in pre-eclamptic than normotensive pregnancies (P<0.05). Immunohistochemical signals of 8-OHdG were detected mainly in syncytiotrophoblasts and vascular endothelial cells, and co-localized with those for IDO. Furthermore, a significant inverse correlation was found between the IDO activity and 8-OhdG levels. These results show that oxidative stress is associated with decreased IDO activity in the pre-eclamptic placenta and suggest an impact of low IDO activity other than immune modulation in promoting the onset of this disorder.