While dysregulation of the kynurenine pathway (KP) has been associated with pathogenesis, a complete loss of the KP can also have detrimental effects. For example, inhibiting indoleamine 2,3-dioxygenase (IDO)-1 during pregnancy results in fetal loss in a mouse model, which is likely driven by the loss of maternal immune tolerance. Furthermore, KP metabolites may also play a role in fetal development, kynurenic acid has been shown to be involved in neural plasticity and brain development.
Since maternal kynurenine levels can impact the developing fetus, Dr. Bruno Pedraz-Petrozzi and colleagues recently investigated tryptophan and KP metabolite levels in the placenta, umbilical cord, and fetal membrane using an LC-MS/MS method. There was a high kynurenine/tryptophan ratio in the placenta compared to the umbilical cord and fetal membrane, which is not surprising as other studies indicate high levels of IDO expression within the placenta. Kynurenine levels are significantly lower in the fetal membrane, whereas kynurenic acid (KYNA) levels are significantly higher than in the placenta. Suggesting that KYNA plays a role in fetal development. Since samples were taken at delivery it is important to remember that local levels of KP metabolites may fluctuate throughout pregnancy. Further research is required to understand how these levels are affected at different gestational stages, as well as by different maternal diseases, such as during peripartum depression.