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Review
. 2024 Apr 22;25(8):4577.
doi: 10.3390/ijms25084577.

The Role of the Placental Enzyme Indoleamine 2,3-Dioxygenase in Normal and Abnormal Human Pregnancy

Yoshiki Kudo  1 , Jun Sugimoto  1
Affiliations
Review

The Role of the Placental Enzyme Indoleamine 2,3-Dioxygenase in Normal and Abnormal Human Pregnancy

Yoshiki Kudo et al. Int J Mol Sci. .

Abstract

The biologically significant phenomenon that the fetus can survive immune attacks from the mother has been demonstrated in mammals. The survival mechanism depends on the fetus and placenta actively defending themselves against attacks by maternal T cells, achieved through the localized depletion of the amino acid L-tryptophan by an enzyme called indoleamine 2,3-dioxygenase. These findings were entirely unexpected and pose important questions regarding diseases related to human pregnancy and their prevention during human pregnancy. Specifically, the role of this mechanism, as discovered in mice, in humans remains unknown, as does the extent to which impaired activation of this process contributes to major clinical diseases in humans. We have, thus, elucidated several key aspects of this enzyme expressed in the human placenta both in normal and abnormal human pregnancy. The questions addressed in this brief review are as follows: (1) localization and characteristics of human placental indoleamine 2,3-dioxygenas; (2) overall tryptophan catabolism in human pregnancy and a comparison of indoleamine 2,3-dioxygenase expression levels between normal and pre-eclamptic pregnancy; (3) controlling trophoblast invasion by indoleamine 2,3-dioxygenase and its relation to the pathogenesis of placenta accrete spectrum.

Keywords: human pregnancy; indoleamine 2,3-dioxygenase; placenta; placenta accreta spectrum; pre-eclampsia; trophoblast.

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Conflict of interest statement

The authors declare that we have no conflict of interest in connection with this paper.

Figures

Figure 1
Figure 1
Structure of tryptophan analogues.
Figure 2
Figure 2
A diagram of catabolic pathways for tryptophan.
Figure 3
Figure 3
Immunohistochemistry of IDO at the maternal–fetal interface of seven weeks of gestation. (A) Implantation site of seven weeks of gestation. (B) Immunohistochemical localization of IDO. Reproduced from Kudo et al. [44]. Scales for images are as indicated.
Figure 4
Figure 4
Immunohistochemical localization of IDO in decidua. (A) HE staining. (B) Immunostaining for IDO (a) and HLA-G (b). Reproduced from Kudo et al. [56]. Scales for images are as indicated.
Figure 5
Figure 5
A schematic representation of the role of placental IDO in human pregnancy. Reproduced from Kudo et al. [50].
See this image and copyright information in PMC

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