PMID- 35219639
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220429
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 440
DP  - 2022 Apr 1
TI  - Cadmium induces placental glucocorticoid barrier damage by suppressing the 
      cAMP/PKA/Sp1 pathway and the protective role of taurine.
PG  - 115938
LID - S0041-008X(22)00083-7 [pii]
LID - 10.1016/j.taap.2022.115938 [doi]
AB  - Cadmium (Cd) exposure during pregnancy damages the placental glucocorticoid (GC) 
      barrier, exposes the foetus to excess corticosterone (CORT) levels, and 
      eventually inhibits foetal development. In addition, taurine (Tau) alleviates the 
      toxicity of Cd on liver and kidney, but limited data are available on the role of 
      Tau against the toxicity of heavy metals on female reproduction and fetal 
      development. The present study was conducted to investigate the specific 
      mechanism of Cd-induced placental GC barrier damage and the protective role of 
      Tau. Pregnant rats were administered CdCl2 (1 mg/kg/day) and Tau (100, 200, or 
      300 mg/kg/day) by gavage from gestational day (GD) 0 to 19. The data showed that 
      CdCl(2) increased the foetal growth restriction (FGR) rate of the offspring, and 
      the levels of CORT in the placental, maternal and foetal serum. Treatment with 
      Tau significantly reversed the impact of Cd on both maternal and fetal 
      parameters. Additionally, Tau can attenuate Cd-induced inhibition of 
      11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) and specificity protein 1 (Sp1) in 
      vivo and vitro. Furthermore, Sp1-siRNA alone reduced 11beta-HSD2 levels and had a 
      further inhibitory effect when the cells were treated with Cd simultaneously. 
      Moreover, Cd suppressed cAMP/PKA signalling. Forskolin (adenylate cyclase 
      agonist) pretreatment activated cAMP/PKA signalling and restored the Cd-induced 
      downregulation of Sp1 and 11beta-HSD2. Tau alleviated the Cd-induced decrease of Sp1 
      via activating cAMP/PKA signalling. Therefore, the results highlight that Tau 
      protects against Cd-induced impairments in GC barrier damage by upregulating the 
      cAMP/PKA/Sp1 pathway in placental trophoblasts.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Chen, Na
AU  - Chen N
AD  - Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; The 
      Second Clinical Medical College of Wenzhou Medical University, Wenzhou City, 
      Zhejiang Province 325000, China.
FAU - Tong, Xia
AU  - Tong X
AD  - Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; The 
      Second Clinical Medical College of Wenzhou Medical University, Wenzhou City, 
      Zhejiang Province 325000, China.
FAU - Wu, Sisi
AU  - Wu S
AD  - Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; The 
      Second Clinical Medical College of Wenzhou Medical University, Wenzhou City, 
      Zhejiang Province 325000, China.
FAU - Xu, Xu
AU  - Xu X
AD  - Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; The 
      Second Clinical Medical College of Wenzhou Medical University, Wenzhou City, 
      Zhejiang Province 325000, China.
FAU - Chen, Qihui
AU  - Chen Q
AD  - Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; The 
      Second Clinical Medical College of Wenzhou Medical University, Wenzhou City, 
      Zhejiang Province 325000, China.
FAU - Wang, Fan
AU  - Wang F
AD  - Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of 
      Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; The 
      Second Clinical Medical College of Wenzhou Medical University, Wenzhou City, 
      Zhejiang Province 325000, China. Electronic address: wf@wzhealth.com.
LA  - eng
PT  - Journal Article
DEP - 20220224
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Glucocorticoids)
RN  - 00BH33GNGH (Cadmium)
RN  - 1EQV5MLY3D (Taurine)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - *11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism
MH  - Animals
MH  - Cadmium/metabolism
MH  - Corticosterone
MH  - Female
MH  - Glucocorticoids/metabolism/pharmacology
MH  - *Placenta/metabolism
MH  - Pregnancy
MH  - Rats
MH  - Taurine/pharmacology
OTO - NOTNLM
OT  - 11beta-HSD2
OT  - Cadmium
OT  - Glucocorticoids
OT  - Sp1
OT  - Taurine
EDAT- 2022/02/28 06:00
MHDA- 2022/04/30 06:00
CRDT- 2022/02/27 20:28
PHST- 2021/07/24 00:00 [received]
PHST- 2022/02/17 00:00 [revised]
PHST- 2022/02/18 00:00 [accepted]
PHST- 2022/02/28 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/02/27 20:28 [entrez]
AID - S0041-008X(22)00083-7 [pii]
AID - 10.1016/j.taap.2022.115938 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2022 Apr 1;440:115938. doi: 10.1016/j.taap.2022.115938. 
      Epub 2022 Feb 24.