Increased mRNA Expression of Kynurenine Pathway Enzymes in Human Placentae Exposed To Bacterial Endotoxin

Abstract

Intra-amniotic bacterial infection is a major risk factor for cerebral impairment in infants that are born pre-term however, the causal pathways are largely unknown’. Whether placental derived, neuroactive kynurenine metabolites play any role in fetal cerebral damage during episodes of intra-amniotic infection is presently unknown. In this preliminary study, we explored if kynurenine metabolites may be involved, examining if mRNAs of enzymes involved in tryptophan catabolism through the kynurenine pathway (KP) were expressed in the placenta and if their expression was co-ordinately altered with exposure to bacterial infection. We found that placentae from healthy women at term and those with clinical signs of amniotic fluid bacterial infection pre-term expressed mRNAs of the KP enzymes, with higher expression overall in the infected group. Significant increases in indoleamine 2,3-dioxygenase (IDO), tryptophan dioxygenase (TDO) and kynureninase (KYNase) expression were detected in association with infection. These findings suggest that tryptophan may be constitutively degraded through the KP in the human placenta. Whether higher concentrations of placental derived kynurenine metabolites enter the fetus during episodes of infection and their physiological roles if any remains to be elucidated.