胎盘
吲哚胺2,3-双加氧酶
生物
犬尿氨酸
胎盘形成
子痫前期
胎儿
内分泌学
怀孕
免疫学
内科学
医学
色氨酸
生物化学
氨基酸
遗传学
作者
Gayathri Guru Murthy,Mallory A. Prideaux,Madison Armstrong,H. Mark Kenney,Sarah E. Latchney,Martha Susiarjo,Shawn P. Murphy
出处
期刊:Placenta
[Elsevier]
日期:2021-11-01
卷期号:115: 129-138
被引量:5
标识
DOI:10.1016/j.placenta.2021.09.008
摘要
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.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.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.Our collective results are consistent with potential role(s) for IDO1 in the regulation of vascular functions in placental villi.
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