Impact of intraamniotic inflammation on tryptophan metabolism in the placenta-fetal brain axis in rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10499794" target="_blank" >RIV/00179906:_____/25:10499794 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/25:00619542 RIV/62690094:18470/25:50022477 RIV/00216208:11160/25:10499794 RIV/00216208:11150/25:10499794

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=BgLZW1bfCn" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=BgLZW1bfCn</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1530/REP-24-0378" target="_blank" >10.1530/REP-24-0378</a>

Result language

angličtina

Original language name

Impact of intraamniotic inflammation on tryptophan metabolism in the placenta-fetal brain axis in rats

Original language description

In brief: Intrauterine inflammation disrupts tryptophan metabolism in both the placenta and the fetal brain, leading to a shift toward neurotoxic metabolites. These findings highlight the critical role of placental function in neurodevelopment and suggest that inflammation-induced metabolic changes may contribute to neurodevelopmental disorders. Abstract: The placenta plays a crucial role beyond nutrient transfer, acting as a dynamic endocrine organ that significantly influences maternal physiology and fetal development. It responds rapidly to even slight changes in the in utero environment to promote fetal survival. Disruptions in placental function are increasingly recognized as key contributors to the origins of neurodevelopmental disorders. In this study, we employed advanced technology to induce intrauterine inflammation through ultrasound-guided administration of LPS into gestational sacs. We then evaluated its effects on the gene expression of enzymes involved in TRP metabolism and conducted a comprehensive LC/MS analysis of the metabolome in the placenta and fetal brain of Wistar rats. Our results show that intraamniotic injection of LPS induces a robust inflammatory response leading to significant alterations in TRP metabolism, including downregulation of tryptophan hydroxylase (TPH) in the placenta, resulting in a decrease in serotonin (5-HT) levels. Similarly, in the fetal brain, exposure to LPS led to reduced Tph expression and increased monoamine oxidase expression, suggesting a decrease in 5-HT synthesis and an increase in its degradation. Furthermore, an upregulation of the kynurenine pathway was observed in both the placenta and fetal brain. Moreover, we detected a shift toward neurotoxicity, evidenced by an imbalance between neuroprotective and neurotoxic metabolites, including decreased levels of kynurenic acid and upregulation of kynurenine monooxygenase in the fetal brain. In conclusion, our findings reveal significant alterations in TRP metabolism following intrauterine inflammation, potentially contributing to neurodevelopmental disorders.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30214 - Obstetrics and gynaecology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Reproduction

ISSN

1470-1626

e-ISSN

1741-7899

Volume of the periodical

169

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

e240378

UT code for WoS article

001518865900002

EID of the result in the Scopus database

2-s2.0-105003923332