Tryptophan’s Journey Through Pregnancy: The Role of Serotonin

Tryptophan is an essential amino acid required for protein synthesis and a precursor of key bioactive metabolites produced through the kynurenine, indole and serotonin pathways. Beyond its nutritional role, tryptophan metabolism critically regulates the nervous, immune and endocrine systems, coordinates circadian rhythms via melatonin, and exerts antioxidant effects. These processes are profoundly remodeled during pregnancy. Pregnancy represents a unique physiological state characterized by systemic adaptations, including changes in immunity and erythropoiesis, while the placenta emerges as a central organ coordinating fetal development, maternal-fetal exchanges, immune tolerance, and protection against external infections. Increasing evidence indicates that tryptophan availability and its downstream metabolites play key roles in maintaining maternal-fetal and placental homeostasis. In particular, serotonin, traditionally viewed as a neurotransmitter, has emerged as a locally produced signaling molecule in the placenta, impacting trophoblast development, placental vascularization, and immune modulation. Dysregulation of tryptophan metabolic pathways has been associated with pregnancy complications and adverse developmental outcomes. This review aims to provide an overview of tryptophan metabolism during gestation, with a specific focus on serotonin as a key factor in placental homeostasis. Targeting tryptophan-derived pathways may offer novel opportunities to improve maternal and neonatal health.