Localisation of Indoleamine 2,3-dioxygenase and Kynurenine Hydroxylase in the Human Placenta and Decidua: Implications for Role of the Kynurenine Pathway in Pregnancy

Indoleamine 2,3-dioxygenase (IDO) has been implicated in contributing to immunotolerance in early pregnancy, but the presence in the term placenta of mRNAs for enzymes that produce other biologically active kynurenine end-products suggests other functions for kynurenine pathway metabolites. The aim of this study was to investigate the localisation of two key enzymes - IDO and kynurenine hydroxylase (KYN-OHase) - in first trimester decidua and in the human placenta across pregnancy. Using immunocytochemistry, it was shown that there was strong expression of IDO and KYN-OHase in stromal and glandular epithelial cells of first trimester decidua. In first and second trimester placenta, IDO and KYN-OHase were localised to the syncytiotrophoblast, stroma and macrophages. IDO and KYN-OHase mRNAs were also identified, and the enzymes appear to be functional because kynurenine and 3-hydroxy-anthranilic acid (respective products of the activity of these enzyme) were released into the medium when first trimester placental explants were maintained in culture for 48 h. In term placenta, both IDO and KYN-OHase immunoreactivities were confined mainly to vascular endothelial cells of villous blood vessels, and to macrophages within the fetal villus, whereas syncytial staining was very weak or absent. The shift of expression of these enzymes away from the syncytiotrophoblast to fetal endothelial cells in terminal villi suggests that the function of the enzymes may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy, to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation.