The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?

(<i>L</i>-)tryptophan is metabolized via the kynurenine pathway into several kynurenine metabolites with distinct functions. Dysfunction of the kynurenine pathway can lead to impairments in vascular regulation, immune regulation, and tolerance. The first and rate limiting enzyme of this...

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Autores principales:	Michelle Broekhuizen, A. H. Jan Danser, Irwin K. M. Reiss, Daphne Merkus
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	tryptophan kynurenine indoleamine 2,3-dioxygenase placenta pregnancy therapy Medicine R
Acceso en línea:	https://doaj.org/article/c2520dc31aab497e8e697138f930e1ec
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spelling	oai:doaj.org-article:c2520dc31aab497e8e697138f930e1ec2021-11-11T16:39:38ZThe Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?10.3390/ijerph1821115451660-46011661-7827https://doaj.org/article/c2520dc31aab497e8e697138f930e1ec2021-11-01T00:00:00Zhttps://www.mdpi.com/1660-4601/18/21/11545https://doaj.org/toc/1661-7827https://doaj.org/toc/1660-4601(<i>L</i>-)tryptophan is metabolized via the kynurenine pathway into several kynurenine metabolites with distinct functions. Dysfunction of the kynurenine pathway can lead to impairments in vascular regulation, immune regulation, and tolerance. The first and rate limiting enzyme of this pathway, indoleamine 2,3-dioxygenase (IDO), is highly expressed in the placenta and reduced in placentas from complicated pregnancies. IDO is essential during pregnancy, as IDO inhibition in pregnant mice resulted in fetal loss. However, the exact function of placental IDO, as well as its exact placental localization, remain controversial. This review identified that two isoforms of IDO; IDO1 and IDO2, are differently expressed between placental cells, suggesting spatial segregation. Furthermore, this review summarizes how the placental kynurenine pathway is altered in pregnancy complications, including recurrent miscarriage, preterm birth, preeclampsia, and fetal growth restriction. Importantly, we describe that these alterations do not affect maternally circulating metabolite concentrations, suggesting that the kynurenine pathway functions as a local signaling pathway. In the placenta, it is an important source of de novo placental NAD<sup>+</sup> synthesis and regulates fetal tryptophan and kynurenine metabolite supply. Therefore, kynurenine pathway interventions might provide opportunities to treat pregnancy complications, and this review discusses how such treatment could affect placental function and pregnancy development.Michelle BroekhuizenA. H. Jan DanserIrwin K. M. ReissDaphne MerkusMDPI AGarticletryptophankynurenineindoleamine 2,3-dioxygenaseplacentapregnancytherapyMedicineRENInternational Journal of Environmental Research and Public Health, Vol 18, Iss 11545, p 11545 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tryptophan kynurenine indoleamine 2,3-dioxygenase placenta pregnancy therapy Medicine R
spellingShingle	tryptophan kynurenine indoleamine 2,3-dioxygenase placenta pregnancy therapy Medicine R Michelle Broekhuizen A. H. Jan Danser Irwin K. M. Reiss Daphne Merkus The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
description	(<i>L</i>-)tryptophan is metabolized via the kynurenine pathway into several kynurenine metabolites with distinct functions. Dysfunction of the kynurenine pathway can lead to impairments in vascular regulation, immune regulation, and tolerance. The first and rate limiting enzyme of this pathway, indoleamine 2,3-dioxygenase (IDO), is highly expressed in the placenta and reduced in placentas from complicated pregnancies. IDO is essential during pregnancy, as IDO inhibition in pregnant mice resulted in fetal loss. However, the exact function of placental IDO, as well as its exact placental localization, remain controversial. This review identified that two isoforms of IDO; IDO1 and IDO2, are differently expressed between placental cells, suggesting spatial segregation. Furthermore, this review summarizes how the placental kynurenine pathway is altered in pregnancy complications, including recurrent miscarriage, preterm birth, preeclampsia, and fetal growth restriction. Importantly, we describe that these alterations do not affect maternally circulating metabolite concentrations, suggesting that the kynurenine pathway functions as a local signaling pathway. In the placenta, it is an important source of de novo placental NAD<sup>+</sup> synthesis and regulates fetal tryptophan and kynurenine metabolite supply. Therefore, kynurenine pathway interventions might provide opportunities to treat pregnancy complications, and this review discusses how such treatment could affect placental function and pregnancy development.
format	article
author	Michelle Broekhuizen A. H. Jan Danser Irwin K. M. Reiss Daphne Merkus
author_facet	Michelle Broekhuizen A. H. Jan Danser Irwin K. M. Reiss Daphne Merkus
author_sort	Michelle Broekhuizen
title	The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
title_short	The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
title_full	The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
title_fullStr	The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
title_full_unstemmed	The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
title_sort	function of the kynurenine pathway in the placenta: a novel pharmacotherapeutic target?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c2520dc31aab497e8e697138f930e1ec
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The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?

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