Identification of kynurenine pathway enzyme mRNAs and metabolites in human placenta: up-regulation by inflammatory stimuli and with clinical infection.
OBJECTIVE
The purpose of this study was to determine whether placental-derived kynurenines (neuroactive metabolites that are derived from tryptophan) contributes to infection-mediated fetal cerebral injury.


METHODS
Placentae and cord blood were obtained from term deliveries (n = 16) and preterm deliveries with or without intrauterine bacterial infection (n = 8 per group). We investigated whether the placenta expressed messenger RNAs of kynurenine metabolite-forming enzymes, the effects of infection in vivo on the expression of these enzymes by the placenta, the in vitro effects of bacterial endotoxin lipopolysaccharide on expression and kynurenine metabolite output by the placenta, and the kynurenine metabolite levels in umbilical cord blood.


RESULTS
Placentae expressed messenger RNA of tryptophan-degrading enzymes and synthesized several compounds. The expression of several enzymes increased significantly in placentae that were exposed to infection and/or lipopolysaccharide. Lipopolysaccharide also induced significant increases in placental kynurenine and quinolinic acid output. Kynurenine and quinolinic acid in cord blood of fetuses who were exposed to infection were elevated significantly.


CONCLUSIONS
Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.
Manuelpillai
Ursula
U
Department of Obstetrics and Gynaecology, Monash University, Clayton, Australia. ursula.manuelpillai@med.monash.edu.au
Ligam
Poonam
P
Smythe
George
G
Wallace
Euan M
EM
Hirst
Jonathan
J
Walker
David W
DW
D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007737:Kynurenine