The role of placental tryptophan catabolism

Abstract

This review discusses the mechanisms and consequences of degradation of tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3-dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of feto-maternal tolerance in the mouse. Local depletion of Trp and/or the presence of metabolites of the kynurenine pathway mediate immunoregulation and exert antimicrobial functions. In addition to the decidual glandular epithelium, IDO1 is localized in the vascular endothelium of the villous chorion and also in the endothelium of spiral arteries of the decidua. Possible consequences of IDO1-mediated catabolism of Trp in the endothelium encompass antimicrobial activity and immunosuppression, as well as relaxation of the placental vasotonus, thereby contributing to placental perfusion and growth of both placenta and fetus. It remains to be evaluated whether other enzymes mediating Trp oxidation, such as indoleamine 2,3-dioxygenase-2, Trp 2,3-dioxygenase, and Trp hydroxylase-1 are of relevance to the biology of the placenta.

Keywords: fetal growth restriction; feto-maternal tolerance; immunoregulation; intrauterine growth restriction; placenta; preeclampsia; pregnancy; vasotonus.

Figure 1

Pathways of Trp degradation.

Figure 2

Schematic drawing of the localization of IDO1 in the human placenta during first trimester pregnancy. The chorionic villus is the structural element involved in feto-maternal exchanges. The stem villi originate from the chorionic plate and ramify into villous branches. They consist of a core of mesenchymal connective tissue containing vessels, which are in contact with the fetal vasculature via the umbilical cord. The chorionic villi are covered by a double layer of villous trophoblast (the upper syncytiotrophoblast and the lower cytotrophoblast) separating the fetal closed blood circulation from the intervillous space, which is filled with maternal blood which is supplied via the uterine spiral arteries (a) and discharged via the uterine veins (v). Some of the villi are anchored into the maternal decidua basalis by roots built of extra-villous cytotrophoblast cells, which also invade the maternal decidua. The IDO1 expression sites are highlighted in red color and refer to the villous subtrophoblastic capillaries, few immune cells of the decidua, and the epithelium of uterine glands.

Figure 3

Schematic drawing of the term placenta with the basal plate after delivery. The structures of placental architecture are described in the legend to Figure 1. Here, the branching of the villous tree has increased, the villous trophoblast is largely reduced to the syncytiotrophoblast. IDO1 protein is indicated by red color broken red lines indicate partial expression. All endothelia of the vessels of the villous chorion express IDO1, while only part of the vessels of the chorionic plate and none of the umbilical cord vessels are positive. Openings of maternal arteries (a) express IDO1 whereas veins do not.