Characterization of the temporal, cell-specific and interferon-inducible patterns of indoleamine 2, 3 dioxygenase 1 (IDO1) expression in the human placenta across gestation. (November 2021)

• Record Type: Journal Article
• Authors: Murthy, Gayathri Guru; Prideaux, Mallory A.; Armstrong, Madison; Kenney, H. Mark; Latchney, Sarah E.; Susiarjo, Martha; Murphy, Shawn P.
• Is Part Of: Placenta. Volume 115(2021)
• Page Start: 129
• Page End: 138
• Publication Date: 2021-11
• Subjects: Placenta -- Endothelial cells -- Indoleamine 2, 3 dioxygenase 1 (IDO1) -- Kynurenine -- Interferons; CK7 cytokeratin 7 -- EVT extravillous trophoblast -- IDO1 indoleamine 2, 3 dioxygenase 1 -- IFN interferon -- IUGR in utero growth restriction -- LPS lipopolysaccharide -- PLEC placental endothelial cells -- RT-qPCR reverse transcriptase-quantitative polymerase chain reaction -- SYN syncytiotrophoblast -- TDO tryptophan 2, 3-dioxygenase -- vCTB villous cytotrophoblast -- WMIF whole mount immunofluorescence; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2021.09.008
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: The human placenta performs multiple functions necessary for successful pregnancy, but the metabolic pathways and molecular mechanisms responsible for regulating placental development and functions remain incompletely understood. Catabolism of the essential amino acid tryptophan has numerous critical roles in normal physiology, including inflammation. The kynurenine pathway, which accounts for ∼90% of tryptophan breakdown, is mediated by indoleamine 2, 3 dioxygenase 1 (IDO1) in the placenta. In pregnant mice, alterations of IDO1 activity or expression result in fetal resorption and a preeclampsia-like phenotype. Decreased IDO1 expression at the maternal-fetal interface has also been linked to preeclampsia, in utero growth restriction and recurrent miscarriage in humans. These collective observations suggest essential role(s) for IDO1 in maintaining healthy pregnancy. Despite these important roles, the precise temporal, cell-specific and inflammatory cytokine-mediated patterns of IDO1 expression in the human placenta have not been thoroughly characterized across gestation. Methods: Western blot and whole mount immunofluorescence (WMIF) were utilized to characterize and quantify basal and interferon (IFN)-inducible IDO1 expression in 1st trimester (7–13 weeks), 2nd trimester (14–22 weeks) and term (39–41 weeks) placental villi. Results: IDO1 expression is activated in the human placenta between the 13th and 14th weeks of pregnancy, increases through the 2nd trimester and remains elevated at term. Constitutive IDO1 expression is restricted to placental endothelial cells. Interestingly, different types of IFNs have distinct effects on IDO1 expression in the human placenta. Discussion: Our collective results are consistent with potential role(s) for IDO1 in the regulation of vascular functions in placental villi. Highlights: IDO1 expression is activated in the human placenta between gestation weeks 13 & 14. Maximal IDO1 expression was observed in placental villi at term. Expression of IDO1 is restricted predominately to placental endothelial cells. Interferons have differential effects on IDO1 expression in the human placenta. IFNγ activated IDO1 expression in placental stromal cells but not trophoblast.