The Role of Placental Tryptophan Catabolism

Sedlmayr, Peter; Blaschitz, Astrid; Stocker, Roland

doi:10.3389/fimmu.2014.00230

Cited by 82 publications

(70 citation statements)

References 123 publications

(167 reference statements)

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“…TRP levels are also raised in the fetal brain when pregnant rats are stressed by crowding during the final week of gestation [38], though, to our knowledge, this effect has so far not been authenticated in mice. Although the underlying mechanism(s) may also include compensatory down-regulation of other TRP-degrading placental enzymes during the prenatal period [39] and/or direct effects of steroid hormones on TRP metabolism [40–42], the elevated TRP levels seen in the highly vascularized placenta [43] immediately after restraint of the dam were more likely related to increased free TRP or to the presence of maternal blood where we observed a trend toward increased TRP levels (Table 2). …”

Section: Discussionmentioning

confidence: 99%

Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain

Notarangelo

Schwarcz²

2016

Dev Neurosci

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Stressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17. TRP, KYN, KYNA, 3-HK, and QUIN levels were measured in maternal and fetal plasma and brain, as well as in the placenta, immediately after stress termination and 2 h later. In the same animals, we determined the activity of TRP 2,3-dioxygenase (TDO) in the maternal liver and in the placenta. Compared to unstressed controls, mostly transient changes in KP metabolism were observed in all of the tissues examined. Specifically, stress caused significant elevations of KYNA levels in the maternal plasma, placenta, and fetal brain, and also resulted in increased levels of TRP and KYN in the placenta, fetal plasma, and fetal brain. In contrast, 3-HK and QUIN levels remained unchanged from control values in all tissues at any time point. In the maternal liver, TDO activity was increased 2 h after stress cessation. Taken together, these findings indicate that an acute stress during the late gestational period preferentially affects the KYNA branch of KP metabolism in the fetal brain. Possible long-term consequences for postnatal brain development and pathology remain to be examined.

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Section: Discussionmentioning

confidence: 99%

Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain

Notarangelo

Schwarcz²

2016

Dev Neurosci

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“…An example of compromised recognition of SCNT conceptuses by the endometrium is the gene encoding the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), which is down-regulated in caruncular tissue (fold change, 0.54; FDR < 0.05) and also tended to be down-regulated in intercaruncular tissue (fold change, 0.67; FDR = 0.08). IDO1 is one of the enzymes responsible for catabolizing tryptophan in a pathway essential for maternal immune tolerance toward the conceptus (37,38). Down-regulation of IDO1 may be directly linked to the reduced likelihood of implantation success in cloned conceptuses.…”

Section: Discussionmentioning

confidence: 99%

Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium

Biase

Rabel

Guillomot

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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A major unresolved issue in the cloning of mammals by somatic cell nuclear transfer (SCNT) is the mechanism by which the process fails after embryos are transferred to the uterus of recipients before or during the implantation window. We investigated this problem by using RNA sequencing (RNA-seq) to compare the transcriptomes in cattle conceptuses produced by SCNT and artificial insemination (AI) at day (d) 18 (preimplantation) and d 34 (postimplantation) of gestation. In addition, endometrium was profiled to identify the communication pathways that might be affected by the presence of a cloned conceptus, ultimately leading to mortality before or during the implantation window. At d 18, the effects on the transcriptome associated with SCNT were massive, involving more than 5,000 differentially expressed genes (DEGs). Among them are 121 genes that have embryonic lethal phenotypes in mice, cause defects in trophoblast and placental development, and/or affect conceptus survival in mice. In endometria at d 18, <0.4% of expressed genes were affected by the presence of a cloned conceptus, whereas at d 34, ∼36% and <0.7% of genes were differentially expressed in intercaruncular and caruncular tissues, respectively. Functional analysis of DEGs in placental and endometrial tissues suggests a major disruption of signaling between the cloned conceptus and the endometrium, particularly the intercaruncular tissue. Our results support a "bottleneck" model for cloned conceptus survival during the periimplantation period determined by gene expression levels in extraembryonic tissues and the endometrial response to altered signaling from clones. somatic cell nuclear transfer | conceptus | placentation | conceptus-maternal communication I n cattle, as in other mammals, exquisitely orchestrated physiological changes of the conceptus and uterus are necessary for a successful pregnancy. Synchronization of the complex events at the time of implantation relies on the timed release of molecular signals from the conceptus and the endometrium. Embryo-derived IFN-τ (IFNT) is the major signal of pregnancy in cattle, preventing luteolysis and regulating the expression of genes that are responsible for promoting local changes in the endometrium to accommodate the conceptus (1-3). In females, progesterone is the major driver of endometrial changes that prepare the uterus for conceptus implantation (4, 5). In addition to IFNT and progesterone, signaling between the bovine conceptus and the endometrium is bidirectional, and involves several pathways that work concomitantly (6) for the successful establishment of pregnancy.Independent studies have shown that the majority of embryonic losses in cattle occur during the period that spans embryo cleavage until the attachment of the blastocyst to the endometrium (7). The reasons for these losses remain unclear and likely result from several factors, including embryonic lethal genes (8, 9), environmental stressors (7), and endometrial condition (10). Cloning of cattle by somatic cell nuclear transfer ...

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“…The interactions of KP metabolites with the aryl hydrocarbon receptor (AhR) are described in more detail in other articles in this issue. The roles of Trp-catabolizing enzymes in the placenta and central nervous system also have been reviewed recently ( 26 , 27 ).…”

Section: Functional Convergence Of Ido and Tdomentioning

confidence: 99%

Tryptophan-Catabolizing Enzymes â€“ Party of Three

et al. 2014

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Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that have independently evolved to catalyze the first step in tryptophan catabolism via the kynurenine pathway (KP). The depletion of tryptophan and formation of KP metabolites modulates the activity of the mammalian immune, reproductive, and central nervous systems. IDO and TDO enzymes can have overlapping or distinct functions depending on their expression patterns. The expression of TDO and IDO enzymes in mammals differs not only by tissue/cellular localization but also by their induction by distinct stimuli. To add to the complexity, these genes also have undergone duplications in some organisms leading to multiple isoforms of IDO or TDO. For example, many vertebrates, including all mammals, have acquired two IDO genes via gene duplication, although the IDO1-like gene has been lost in some lower vertebrate lineages. Gene duplications can allow the homologs to diverge and acquire different properties to the original gene. There is evidence for IDO enzymes having differing enzymatic characteristics, signaling properties, and biological functions. This review analyzes the evolutionary convergence of IDO and TDO enzymes as tryptophan-catabolizing enzymes and the divergent evolution of IDO homologs to generate an enzyme family with diverse characteristics not possessed by TDO enzymes, with an emphasis on the immune system.

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The Role of Placental Tryptophan Catabolism

Cited by 82 publications

References 123 publications

Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain

Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain

Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium

Tryptophan-Catabolizing Enzymes â€“ Party of Three

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