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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30214 - Obstetrics and gynaecology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Reproduction

ISSN

1470-1626

e-ISSN

1741-7899

Svazek periodika

169

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

e240378

Kód UT WoS článku

001518865900002

EID výsledku v databázi Scopus

2-s2.0-105003923332