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

Michelle Broekhuizen, A. H. Jan Danser, Irwin K. M. Reiss and Daphne Merkus
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Michelle Broekhuizen: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
A. H. Jan Danser: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
Irwin K. M. Reiss: Division of Neonatology, Department of Pediatrics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
Daphne Merkus: Division of Experimental Cardiology, Department of Cardiology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands

IJERPH, 2021, vol. 18, issue 21, 1-23

Abstract: ( L -)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 + 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.

Keywords: tryptophan; kynurenine; indoleamine 2,3-dioxygenase; placenta; pregnancy; therapy (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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