Fetal growth is dependent on substrate supply, which is dependent on substrate transport and its regulation by the placenta, and placental insufficiency contributes to altered maternal-fetal amino acid transfer, and thereby to poor fetal growth. An important placental function is the uptake of tryptophan and its metabolism to serotonin and kynurenine metabolites, which are essential for increased protein synthesis, fetal neuronal growth, and immune function. Whether these particular processes are affected in placental insufficiency leading to fetal growth restriction (FGR) has not been fully elucidated. We hypothesised that tryptophan metabolic pathway and serotonin signalling will be disrupted in FGR.
Using placentae collected from third trimester idiopathic FGR (n=20) and gestation-matched control pregnancies (n=15) relative mRNA expression of tryptophan metabolic pathway genes was assessed using Fluidigm single-cell DNAseq and TaqMan chemistry (Thermo Fisher Scientific). Data were analysed using Mann-Whitney test.
mRNA of the tryptophan metabolising enzymes IDO-1/2 and TDO-2, serotonin synthesis enzyme TPH-1, serotonin transporter SERT1 & 2; and serotonin receptors HTR5A and HTRB5 were detected in all human placental samples. IDO-1, TPH-1 and SERT-1 mRNA expressions were significantly decreased in FGR placentae (p<0.05), while HTRB5 receptor mRNA was significantly increased in FGR compared to control (p<0.01).
This is the first study to report the presence of mRNA for the tryptophan and serotonin metabolic pathways in FGR placentae. These findings suggest that placental metabolism of tryptophan and serotonin is disrupted in FGR.