PMID- 34411824
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240220
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 224
DP  - 2021 Aug 16
TI  - Gestational cadmium exposure impairs placental angiogenesis via activating GC/GR 
      signaling.
PG  - 112632
LID - S0147-6513(21)00744-2 [pii]
LID - 10.1016/j.ecoenv.2021.112632 [doi]
AB  - Gestational exposure to environmental Cd caused placental angiogenesis impairment 
      and fetal growth restriction (FGR). However, its mechanism remained unclear. This 
      study was to investigate the effects of Cd exposure during pregnancy on placental 
      angiogenesis and its mechanism. Pregnant mice were exposed to CdCl(2) (4.5 mg/kg) 
      on gestational day (GD) 8 with or without melatonin (MT) (5.0 mg/kg), an 
      anti-endoplasmic reticulum stress agent, from GD7 to GD15. Human primary 
      placental trophoblasts and JEG-3 cells were stimulated using CdCl(2) (20 muM) 
      after MT (1 mM) preprocessing. We firstly found MT treatment obviously mitigated 
      environmental Cd-induced placental angiogenesis disorder and reduction of the 
      VEGF-A level. Mechanistically, MT reversed environmental Cd-downregulated the 
      protein expression of VEGF-A via inhibiting glucocorticoid receptor (GR) 
      activation. Notably, our data showed MT treatment antagonized Cd-activated GC/GR 
      signaling via blocking PERK signaling and thereby upregulated VEGF-A and 11beta-HSD2 
      protein expression. Based upon the population case-control study, the levels of 
      VEGF-A and 11beta-HSD2 protein in small-for-gestational-age placentae were 
      significantly reduced when compared to appropriate-for-gestational-age placentae. 
      Overall, environmental Cd exposure during gestation impaired placental 
      angiogenesis via PERK-regulated GC/GR signaling in placental trophoblasts. Our 
      findings will provide a basis for prevention and treatment of placental 
      impairments and fetal growth restriction caused by environment toxicants in 
      future.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Shi, Xue-Ting
AU  - Shi XT
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Zhu, Hua-Long
AU  - Zhu HL
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Xu, Xiao-Feng
AU  - Xu XF
AD  - Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First 
      Affiliated Hospital of Anhui Medical University, China; NHC Key Laboratory of 
      Study on Abnormal Gametes and Reproductive Tract, Anhui, China.
FAU - Xiong, Yong-Wei
AU  - Xiong YW
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Dai, Li-Min
AU  - Dai LM
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Zhou, Guo-Xiang
AU  - Zhou GX
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Liu, Wei-Bo
AU  - Liu WB
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Zhang, Yu-Feng
AU  - Zhang YF
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China.
FAU - Wang, Hua
AU  - Wang H
AD  - Department of Toxicology, School of Public Health, Anhui Medical University, 
      China; Key Laboratory of Environmental Toxicology of Anhui Higher Education 
      Institutes, China. Electronic address: wanghuadev@ahmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210816
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
SB  - IM
OTO - NOTNLM
OT  - Cadmium
OT  - Fetal growth restriction
OT  - Glucocorticoid receptor
OT  - Melatonin
OT  - Placental angiogenesis
EDAT- 2021/08/20 06:00
MHDA- 2021/08/20 06:01
CRDT- 2021/08/19 20:20
PHST- 2021/05/23 00:00 [received]
PHST- 2021/08/07 00:00 [revised]
PHST- 2021/08/10 00:00 [accepted]
PHST- 2021/08/20 06:01 [medline]
PHST- 2021/08/20 06:00 [pubmed]
PHST- 2021/08/19 20:20 [entrez]
AID - S0147-6513(21)00744-2 [pii]
AID - 10.1016/j.ecoenv.2021.112632 [doi]
PST - aheadofprint
SO  - Ecotoxicol Environ Saf. 2021 Aug 16;224:112632. doi: 
      10.1016/j.ecoenv.2021.112632.