PMID- 32044612
OWN - NLM
STAT- MEDLINE
DCOM- 20200710
LR  - 20200710
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 261
DP  - 2020 Jun
TI  - Sp1 participates in the cadmium-induced imbalance of the placental glucocorticoid 
      barrier by suppressing 11beta-HSD2 expression.
PG  - 113976
LID - S0269-7491(19)35381-3 [pii]
LID - 10.1016/j.envpol.2020.113976 [doi]
AB  - Cadmium (Cd) is widely present in the environment as a heavy metal poison. 
      Prenatal Cd exposure can damage the placental glucocorticoid barrier, leading to 
      foetal growth restriction (FGR), but the molecular mechanism is unknown. We aimed 
      to study the effects of prenatal Cd exposure on 11beta-HSD2 and its possible 
      involvement in Cd induced damage in the placental glucocorticoid barrier. 
      Pregnant rats were treated with CdCl2 (1.0 mg/kg/day) by gavage from gestational 
      day (GD) 9-19. Maternal exposure to Cd increased the FGR rate of the offspring, 
      and the levels of corticosterone in the placenta, maternal and foetal serum. 
      Further in vitro experiments with placenta or JEG3 cells indicated that Cd was 
      able to decrease 11beta-HSD2 and Sp1 expression in trophoblast cells but did not 
      affect 11beta-HSD1. Additionally, decreased p300 and Sp1 enrichment at the 11beta-HSD2 
      promoter region was observed in the cells treated with Cd. Decreasing or 
      increasing Sp1 expression accordingly inhibited or promoted the expression of 
      11beta-HSD2 and further decreased or increased p300 and Sp1 enrichment at the 
      11beta-HSD2 promoter region. In conclusion, Cd inhibits the expression of 11beta-HSD2 
      by affecting the binding of p300 to 11beta-HSD2 via a decrease in Sp1 expression, 
      which damages the placental glucocorticoid barrier and exposes the foetus to 
      excessive glucocorticoids, resulting in FGR. These findings reveal a possible 
      underlying molecular mechanism by which Cd exposure leads to FGR.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Fan, Fengyun
AU  - Fan F
AD  - Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical 
      College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
FAU - Shen, Wanting
AU  - Shen W
AD  - Departments of Obstetrics and Gynecology, The First Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China; The First Clinical Medical 
      College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
FAU - Wu, Sisi
AU  - Wu S
AD  - Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical 
      College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
FAU - Chen, Na
AU  - Chen N
AD  - Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical 
      College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
FAU - Tong, Xia
AU  - Tong X
AD  - Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical 
      College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
FAU - Wang, Fan
AU  - Wang F
AD  - Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical 
      College, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic 
      address: wf@wzhealth.com.
FAU - Zhang, Qiong
AU  - Zhang Q
AD  - Departments of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou, Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20200122
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (Glucocorticoids)
RN  - 00BH33GNGH (Cadmium)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
SB  - IM
MH  - *11-beta-Hydroxysteroid Dehydrogenase Type 2
MH  - Animals
MH  - Cadmium
MH  - Cell Line, Tumor
MH  - Female
MH  - *Glucocorticoids
MH  - Placenta
MH  - Pregnancy
MH  - Rats
OTO - NOTNLM
OT  - 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2)
OT  - Glucocorticoids
OT  - Placenta
OT  - Prenatal cadmium exposure
OT  - Specificity protein 1(Sp1)
EDAT- 2020/02/12 06:00
MHDA- 2020/07/11 06:00
CRDT- 2020/02/12 06:00
PHST- 2019/09/19 00:00 [received]
PHST- 2019/12/10 00:00 [revised]
PHST- 2020/01/11 00:00 [accepted]
PHST- 2020/02/12 06:00 [pubmed]
PHST- 2020/07/11 06:00 [medline]
PHST- 2020/02/12 06:00 [entrez]
AID - S0269-7491(19)35381-3 [pii]
AID - 10.1016/j.envpol.2020.113976 [doi]
PST - ppublish
SO  - Environ Pollut. 2020 Jun;261:113976. doi: 10.1016/j.envpol.2020.113976. Epub 2020 
      Jan 22.