PMID- 34166751
OWN - NLM
STAT- MEDLINE
DCOM- 20210805
LR  - 20210805
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 458
DP  - 2021 Jun 30
TI  - Disturbance of the Dlk1-Dio3 imprinted domain may underlie placental Dio3 
      suppression and extracellular thyroid hormone disturbance in placenta-derived 
      JEG-3 cells following decabromodiphenyl ether (BDE209) exposure.
PG  - 152837
LID - S0300-483X(21)00160-8 [pii]
LID - 10.1016/j.tox.2021.152837 [doi]
AB  - Decabromodiphenyl ether (BDE209) has been widely used as a flame retardant in the 
      past four decades, leading to human health consequences, especially neurological 
      impairments. Our previous in vivo studies have suggested that developmental 
      neurotoxicity in offspring may be the result of BDE209-induced placental type III 
      iodothyronine deiodinase (Dio3) disturbance and consequent thyroid hormone (TH) 
      instability. Dio3 is paternally imprinted gene, and its balanced expression is 
      crucial in directing normal development and growth. In this study, we used 
      placenta-derived cells to investigate how BDE209 affected Dio3 expression through 
      interfering imprinting mechanisms in the delta-like homolog 1 (Dlk1)-Dio3 
      imprinted region. Gene chip analysis and RT-qPCR identified miR409-3p, miR410-5p, 
      miR494-3p, miR668-3p and miR889-5p as potential candidates involved in Dio3 
      deregulation. The sodium bisulfite-clonal sequencing revealed the BDE209 affect 
      methylation status of two differentially methylated regions (DMRs), 
      intergenic-DMR (IG-DMR) and maternally expressed gene 3-DMR (MEG3-DMR). Our data 
      indicate that placental Dio3 may be a potential molecular target for future study 
      of BDE209 developmental toxicity. In particular, miRNAs, IG-DMR and MEG3-DMR in 
      the Dlk1-Dio3 imprinted locus may be informative in directing studies in TH 
      disturbance and developmental toxicity induced by in utero exposure to 
      environmental persistent organic pollutants (POPs), and those candidate miRNAs 
      may prove to be convenient and noninvasive biomarkers for future large-scale 
      population studies.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Qin, Chang
AU  - Qin C
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Cheng, Ying
AU  - Cheng Y
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China; Zhongshan College of 
      Dalian Medical University, Dalian, 116085, China.
FAU - Shang, Xiaona
AU  - Shang X
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Wang, Ruijun
AU  - Wang R
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Wang, Ruonan
AU  - Wang R
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Hao, Xiaoji
AU  - Hao X
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Li, Sisi
AU  - Li S
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Wang, Ye
AU  - Wang Y
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Li, Yachen
AU  - Li Y
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China.
FAU - Liu, Xiaohui
AU  - Liu X
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China. Electronic address: 
      liuxh892@126.com.
FAU - Shao, Jing
AU  - Shao J
AD  - School of Public Health, Department of Occupational and Environmental Health 
      Sciences, Dalian Medical University, Dalian, 116044, China; Liaoning Key 
      Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, 
      Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Dalian Key 
      Laboratory of Hematology, Diamond Bay Institute of Hematology, Second Hospital of 
      Dalian Medical University, Dalian, Liaoning, 116027, China. Electronic address: 
      jshao@u.washington.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210621
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (DLK1 protein, human)
RN  - 0 (Flame Retardants)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 0 (Membrane Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Thyroid Hormones)
RN  - EC 1.11.1.- (iodothyronine deiodinase type III)
RN  - EC 1.11.1.8 (Iodide Peroxidase)
RN  - N80BQ29A0H (decabromobiphenyl ether)
SB  - IM
EIN - Toxicology. 2021 Jul 20;:152870. PMID: 34301425
MH  - Calcium-Binding Proteins/*drug effects
MH  - Cell Line, Tumor
MH  - DNA Methylation
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Space/*drug effects/*metabolism
MH  - Female
MH  - Flame Retardants/*toxicity
MH  - Gene Expression Regulation, Developmental
MH  - Halogenated Diphenyl Ethers/*toxicity
MH  - Humans
MH  - Iodide Peroxidase/*drug effects
MH  - Membrane Proteins/*drug effects
MH  - MicroRNAs/metabolism
MH  - Placenta/*drug effects/*metabolism
MH  - Pregnancy
MH  - Thyroid Hormones/*metabolism
MH  - Transfection
OTO - NOTNLM
OT  - Decabromodiphenyl ether (BDE209)
OT  - Differentially methylated regions (DMRs)
OT  - Dlk1-Dio3 imprinted domain
OT  - MicroRNAs (miRNAs)
OT  - Placenta-derived cells
OT  - Type III iodothyronine deiodinase (Dio3)
EDAT- 2021/06/25 06:00
MHDA- 2021/08/06 06:00
CRDT- 2021/06/24 20:11
PHST- 2021/03/23 00:00 [received]
PHST- 2021/05/29 00:00 [revised]
PHST- 2021/06/16 00:00 [accepted]
PHST- 2021/06/25 06:00 [pubmed]
PHST- 2021/08/06 06:00 [medline]
PHST- 2021/06/24 20:11 [entrez]
AID - S0300-483X(21)00160-8 [pii]
AID - 10.1016/j.tox.2021.152837 [doi]
PST - ppublish
SO  - Toxicology. 2021 Jun 30;458:152837. doi: 10.1016/j.tox.2021.152837. Epub 2021 Jun 
      21.