PMID- 24709672
OWN - NLM
STAT- MEDLINE
DCOM- 20140706
LR  - 20211021
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 277
IP  - 2
DP  - 2014 Jun 1
TI  - Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates capacity 
      of hematopoietic stem cells to undergo lymphocyte differentiation.
PG  - 172-82
LID - S0041-008X(14)00116-1 [pii]
LID - 10.1016/j.taap.2014.03.020 [doi]
AB  - The process of hematopoiesis, characterized by long-term self-renewal and 
      multi-potent lineage differentiation, has been shown to be regulated in part by 
      the ligand-activated transcription factor known as the aryl hydrocarbon receptor 
      (AHR). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ubiquitous contaminant and 
      the most potent AHR agonist, also modulates regulation of adult hematopoietic 
      stem and progenitor cell (HSC/HPC) homeostasis. However, the effect of 
      developmental TCDD exposure on early life hematopoiesis has not been fully 
      explored. Given the inhibitory effects of TCDD on hematopoiesis and lymphocyte 
      development, we hypothesized that in utero exposure to TCDD would alter the 
      functional capacity of fetal HSC/HPCs to complete lymphocyte differentiation. To 
      test this hypothesis, we employed a co-culture system designed to facilitate the 
      maturation of progenitor cells to either B or T lymphocytes. Furthermore, we 
      utilized an innovative limiting dilution assay to precisely quantify differences 
      in lymphocyte differentiation between HSC/HPCs obtained from fetuses of dams 
      exposed to 3mug/kg TCDD or control. We found that the AHR is transcribed in yolk 
      sac hematopoietic cells and is transcriptionally active as early as gestational 
      day (GD) 7.5. Furthermore, the number of HSC/HPCs present in the fetal liver on 
      GD 14.5 was significantly increased in fetuses whose mothers were exposed to TCDD 
      throughout pregnancy. Despite this increase in HSC/HPC cell number, B and T 
      lymphocyte differentiation is decreased by approximately 2.5 fold. These findings 
      demonstrate that inappropriate developmental AHR activation in HSC/HPCs adversely 
      impacts lymphocyte differentiation and may have consequences for lymphocyte 
      development in the bone marrow and thymus later in life.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Ahrenhoerster, Lori S
AU  - Ahrenhoerster LS
AD  - Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, USA; 
      Program in Environmental and Occupational Health, Milwaukee, WI 53211, USA.
FAU - Tate, Everett R
AU  - Tate ER
AD  - Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, USA; 
      Program in Environmental and Occupational Health, Milwaukee, WI 53211, USA.
FAU - Lakatos, Peter A
AU  - Lakatos PA
AD  - Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, USA; 
      Program in Environmental and Occupational Health, Milwaukee, WI 53211, USA.
FAU - Wang, Xuexia
AU  - Wang X
AD  - Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, USA; 
      Program in Biostatistics, Milwaukee, WI 53211, USA.
FAU - Laiosa, Michael D
AU  - Laiosa MD
AD  - Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, USA; 
      Program in Environmental and Occupational Health, Milwaukee, WI 53211, USA. 
      Electronic address: laiosa@uwm.edu.
LA  - eng
GR  - P30 ES004184/ES/NIEHS NIH HHS/United States
GR  - R00 ES016585/ES/NIEHS NIH HHS/United States
GR  - R00ES016585/ES/NIEHS NIH HHS/United States
GR  - P30ES004184/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140404
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Ahr protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*drug effects/immunology/metabolism/pathology
MH  - Basic Helix-Loop-Helix Transcription Factors/agonists/genetics/metabolism
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dose-Response Relationship, Drug
MH  - Environmental Pollutants/*toxicity
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Gestational Age
MH  - Hematopoietic Stem Cells/*drug effects/immunology/metabolism/pathology
MH  - Lymphocyte Count
MH  - Maternal Exposure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Receptors, Aryl Hydrocarbon/agonists/genetics/metabolism
MH  - T-Lymphocytes/*drug effects/immunology/metabolism/pathology
MH  - Thymocytes/drug effects/pathology
MH  - Time Factors
MH  - Transcription, Genetic/drug effects
PMC - PMC4083512
MID - NIHMS584440
OTO - NOTNLM
OT  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin
OT  - Aryl hydrocarbon receptor
OT  - Developmental immunotoxicology
OT  - Hematopoiesis
OT  - Limiting dilution analysis
OT  - Lymphocyte differentiation
EDAT- 2014/04/09 06:00
MHDA- 2014/07/07 06:00
PMCR- 2015/06/01
CRDT- 2014/04/09 06:00
PHST- 2014/02/06 00:00 [received]
PHST- 2014/03/17 00:00 [revised]
PHST- 2014/03/22 00:00 [accepted]
PHST- 2014/04/09 06:00 [entrez]
PHST- 2014/04/09 06:00 [pubmed]
PHST- 2014/07/07 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - S0041-008X(14)00116-1 [pii]
AID - 10.1016/j.taap.2014.03.020 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2014 Jun 1;277(2):172-82. doi: 
      10.1016/j.taap.2014.03.020. Epub 2014 Apr 4.