The kynurenine pathway (KP) plays a vital role during pregnancy by protecting the fetus from the mother’s immune system. This protective role is facilitated by trophoblast cells in the placenta, which significantly increases the expression of the enzyme IDO. This leads to a decrease in tryptophan (TRP) levels and an increase in the production of kynurenine (KYN), helping to suppress immune cell activity and creating a safe environment for fetal development. Beyond immune tolerance, the KP contributes to fetal growth. Previous research has shown distinct patterns of KP metabolites in the placenta and fetal membrane. with lower KYN levels and higher kynurenic acid (KYNA) levels in the fetal membrane, underscoring KYNA’s significant role in fetal growth (see August 2023 highlight).
Expanding on this insight, Dr. Sofie Van Zundert and colleagues highlight the complex relationship between TRP metabolism, maternal stress, and vulnerability, emphasizing their implications for fetal development. Specifically, the study investigated the impact of maternal vulnerability (i.e., social, lifestyle, or medical risk factors that impair the women’s health) on stress biomarkers and first-trimester growth. Their research revealed that a higher maternal vulnerability risk score during the periconception period correlated with increased levels of stress hormones (hair cortisol and cortisone) and lower TRP levels in the first trimester of pregnancy. Additionally, chronic stress, reflected by elevated cortisol, was linked to reduced fetal growth in the first trimester. TRP, however, did not mediate the relationship between cortisol levels and early fetal growth. This suggests that maternal vulnerability affects both stress and TRP metabolism independently, with little interaction between these processes.
These findings suggest that the chronic stress response and alterations in maternal TRP metabolism are key factors related to maternal vulnerability, which can affect fetal growth and potentially impact the long-term health of the offspring. The study explored the biological mechanisms underlying maternal vulnerability, highlighting potential pathways for prediction, prevention, and personalized medicine. Importantly, early identification of highly vulnerable mothers offers a valuable opportunity for timely interventions, which could significantly improve pregnancy outcomes and the long-term health of their children.