Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.

• Klíčová slova
• fetal brain development, intrauterine infections, placenta, programming, tryptophan metabolism,
• MeSH
• indolamin-2,3,-dioxygenasa metabolismus   MeSH
• kynurenin * metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• placenta * metabolismus   MeSH
• poly I metabolismus   MeSH
• serotonin metabolismus   MeSH
• těhotenství MeSH
• tryptofan metabolismus   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• indolamin-2,3,-dioxygenasa MeSH
• kynurenin * MeSH
• lipopolysacharidy MeSH
• poly I MeSH
• serotonin MeSH
• tryptofan MeSH

Intraamniotic infections caused by viruses, bacteria or mycoplasmas are frequently followed by damage of fetus or increased perinatal morbidity and mortality. Cytokines are key substances regulating a number of biological processes including reproductive and inflammatory processes. An association between intraamniotic infections, rising concentrations of inflammatory cytokines in amniotic fluid and preterm labor is suggested. A great effort is made to find reliable markers typical for intraamniotic infections with high predictive value that make possible prompt identification of patients with intraamniotic infection. This review concerns inflammatory mediators, especially IL-1, IL-6, IL-8, TNF-alpha, and other important biologically active substances as prostaglandins and NO metabolites and their roles in intraamniotic infections. Finally, we discuss their relevance for diagnosis of intraamniotic infections.

• MeSH
• amnion * imunologie   mikrobiologie   MeSH
• bakteriální infekce imunologie   mikrobiologie   MeSH
• cytokiny analýza   fyziologie   MeSH
• gestační stáří MeSH
• infekční komplikace v těhotenství imunologie   mikrobiologie   MeSH
• lidé MeSH
• mediátory zánětu analýza   fyziologie   MeSH
• plodová voda imunologie   mikrobiologie   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• mediátory zánětu MeSH