PMID- 35182797
OWN - NLM
STAT- MEDLINE
DCOM- 20220315
LR  - 20220315
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 233
DP  - 2022 Mar 15
TI  - Gestational exposure to BDE-209 induces placental injury via the endoplasmic 
      reticulum stress-mediated PERK/ATF4/CHOP signaling pathway.
PG  - 113307
LID - S0147-6513(22)00147-6 [pii]
LID - 10.1016/j.ecoenv.2022.113307 [doi]
AB  - Several epidemiological studies have reported significant associations between 
      prenatal polybrominated diphenyl ethers (PBDEs) exposure and adverse birth 
      outcomes. Placental injury is thought to mediate these associations. However, few 
      study has investigated the adverse effects of PBDEs exposure on placental growth 
      and development. We examined the impacts of gestational exposure to BDE-209, the 
      most abundant PBDE conger detected in human samples, on placental structure and 
      function, and its model of action in vivo and in vitro. Pregnant mice were 
      exposed to 0, 2, 20, 200 mg/kg/day of BDE-209 by gavages from gestational day 
      (GD) 0 to GD18. Results showed that gestational BDE-209 exposure significantly 
      reduced placental weight, impaired placental vascular development and induced 
      placental cell apoptosis. In addition, gestational BDE-209 exposure impaired 
      placental transport and endocrine function as demonstrated by markedly 
      downregulated expression of Glut1, Znt1, Pgf and Igf2 in BDE-209-treated 
      placentas. Mechanistically, gestational exposure to BDE-209 upregulated the 
      expression of GRP78, and 3 downstream proteins (p-eIF2alpha, ATF4 and CHOP) of the 
      PERK signaling, suggesting the activation of endoplasmic reticulum (ER) stress 
      and PERK signaling pathway in mouse placentas. Further in vitro study showed that 
      PERK siRNA pretreatment markedly reversed BDE-209-induced cell apoptosis in human 
      JEG-3 cells. Collectively, our results suggest that the activation of the ER 
      stress-mediated PERK/ATF4/CHOP signaling pathway played a role in BDE-209-induced 
      placental injury. Our findings provide new insight into the mechanisms of BDE-209 
      induced reproductive and developmental toxicity.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Zhao, Yan
AU  - Zhao Y
AD  - Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and 
      Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
FAU - Fan, Kechen
AU  - Fan K
AD  - Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and 
      Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
FAU - Zhu, Yan
AU  - Zhu Y
AD  - Obstetrics and Gynecology Department, Songjiang Maternal and Child Health-Care 
      Hospital, Shanghai, China.
FAU - Zhao, Yongbo
AU  - Zhao Y
AD  - Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and 
      Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
FAU - Cai, Jing
AU  - Cai J
AD  - School of Public Health, Key Lab of Public Health Safety of the Ministry of 
      Education and NHC Key Laboratory of Health Technology Assessment, Fudan 
      University, Shanghai, China.
FAU - Jin, Liping
AU  - Jin L
AD  - Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and 
      Infant Hospital, School of Medicine, Tongji University, Shanghai, China. 
      Electronic address: jinlp01@163.com.
LA  - eng
PT  - Journal Article
DEP - 20220216
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - N80BQ29A0H (decabromobiphenyl ether)
SB  - IM
MH  - Activating Transcription Factor 4/genetics/metabolism/pharmacology
MH  - Animals
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - *Endoplasmic Reticulum Stress
MH  - Female
MH  - *Halogenated Diphenyl Ethers/metabolism/toxicity
MH  - Mice
MH  - Placenta/metabolism
MH  - Pregnancy
MH  - Signal Transduction
MH  - Transcription Factor CHOP/genetics/metabolism
MH  - eIF-2 Kinase/metabolism/pharmacology
OTO - NOTNLM
OT  - BDE-209
OT  - Endoplasmic reticulum stress
OT  - Gestational exposure
OT  - PERK/ATF4/CHOP
OT  - Placental injury
EDAT- 2022/02/20 06:00
MHDA- 2022/03/16 06:00
CRDT- 2022/02/19 20:10
PHST- 2021/11/23 00:00 [received]
PHST- 2022/02/09 00:00 [revised]
PHST- 2022/02/10 00:00 [accepted]
PHST- 2022/02/20 06:00 [pubmed]
PHST- 2022/03/16 06:00 [medline]
PHST- 2022/02/19 20:10 [entrez]
AID - S0147-6513(22)00147-6 [pii]
AID - 10.1016/j.ecoenv.2022.113307 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2022 Mar 15;233:113307. doi: 
      10.1016/j.ecoenv.2022.113307. Epub 2022 Feb 16.