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

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.

Systematics of a survivor: the Cambrian kingstoniid trilobite Blountia Walcott, 1916 across the Marjuman-Steptoean (Guzhangian-Paibian) extinction interval in Laurentian North America.

The Cambrian (Marjuman-Steptoean; Guzhangian-Paibian) kingstoniid trilobite Blountia Walcott, 1916 is distributed widely in shelf strata of Laurentian North America. Species known from Marjuman formations were lost at the mass extinction at the end of that stage. New species entered the succession during and after the extinction interval, only to disappear within the Aphelaspis Zone of the lower part of the Steptoean Stage. Steptoean species and several uppermost Marjuman (Crepicephalus Zone) species are treated in this monograph. New collections and revision of type and other archival material increase the number of species in Steptoean strata from two to six. Phylogenetic analysis supports monophyly of Blountia and Maryvillia Walcott, 1916; Blountina Lochman, in Lochman Duncan, 1944 is retained as a monotypic taxon. Steptoean species do not form a single subclade within the cladogram, so there is no evidence for a simple monophyletic radiation following the end-Marjuman extinction. New species are Blountia angelae, B. morgancreekensis, B. nevadensis, B. newfoundlandensis, and B. tennesseensis.