ArticleEnvironmental health perspectives2016
Effects of Developmental Activation of the Aryl Hydrocarbon Receptor by 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Long-term Self-renewal of Murine Hematopoietic Stem Cells.
Article in Environmental health perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Aryl hydrocarbon receptor is involved in DNA damage repair after liver injury with diethylnitrosamine in mice.Molecular biomedicine · 2026Article
- AHR is a master regulator of diverse pathways in endogenous metabolism.Scientific reports · 2022Article
- Aryl Hydrocarbon Receptor: From Homeostasis to Tumor Progression.Frontiers in cell and developmental biology · 2022Review
- The aryl hydrocarbon receptor promotes differentiation during mouse preimplantational embryo development.Stem cell reports · 2021Article
- Converging Roles of the Aryl Hydrocarbon Receptor in Early Embryonic Development, Maintenance of Stemness, and Tissue Repair.Toxicological sciences : an official journal of the Society of Toxicology · 2021Review
- Reducing TGF-β1 cooperated with StemRegenin 1 promoted the expansion ex vivo of cord blood CD34Cell proliferation · 2021Article
- Effects of environmental stressors on stem cells.World journal of stem cells · 2019Review
- AhR signaling pathways and regulatory functions.Biochimie open · 2018Review
- Prenatal exposure to TCDD and atopic conditions in the Seveso second generation: a prospective cohort study.Environmental health : a global access science source · 2018Article
- Does the Aryl Hydrocarbon Receptor Regulate Pluripotency?Current opinion in toxicology · 2017Article
- New Trends in Aryl Hydrocarbon Receptor Biology.Frontiers in cell and developmental biology · 2016Review
- The Aryl Hydrocarbon Receptor Relays Metabolic Signals to Promote Cellular Regeneration.Stem cells international · 2016Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHuman epidemiological and animal studies suggest that developmental exposure to contaminants that activate the aryl hydrocarbon receptor (AHR) lead to suppression of immune system function throughout life. The persistence of immune deficiency throughout life suggests that the cellular target of AHR activation is a fetal hematopoietic progenitor or stem cell.
objectivesThe aim of this study was to identify the effects of transplacental exposure to an AHR agonist on long-term self-renewal of fetal hematopoietic stem cells.
methodsPregnant C57BL/6 or AHR+/- mice were exposed to the AHR agonist, 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD). On day 14 of gestation, hematopoietic progenitors from wild-type or AHR-deficient fetuses were placed into in vitro T-lymphocyte differentiation cultures to identify the effects of transplacental TCDD on AHR activation in the fetus. We next analyzed the fetal hematopoietic progenitor cells for changes in reactive oxygen species (ROS). Finally, hematopoietic progenitors from fetuses exposed transplacentally to TCDD were mixed 1:1 with cells from congenic controls and used to reconstitute lethally irradiated recipients for analysis of long-term self-renewal potential.
resultsOur findings suggested that the effects of TCDD on the developing hematopoietic system were mediated by direct AHR activation in the fetus. Furthermore, developmental AHR activation by TCDD increased ROS in the fetal hematopoietic stem cells, and the elevated ROS was associated with a reduced capacity of the TCDD-exposed fetal cells to compete with control cells in a mixed competitive irradiation/reconstitution assay.
conclusionsOur findings indicate that AHR activation by TCDD in the fetus during pregnancy leads to impairment of long-term self-renewal of hematopoietic stem cells. CITATION: Laiosa MD, Tate ER, Ahrenhoerster LS, Chen Y, Wang D. 2016. Effects of developmental activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin on long-term self-renewal of murine hematopoietic stem cells. Environ Health Perspect 124:957-965; http://dx.doi.org/10.1289/ehp.1509820.
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