Cadmium induces placental glucocorticoid barrier damage by suppressing the cAMP/PKA/Sp1 pathway and the protective role of taurine.
Toxicol Appl Pharmacol
; 440: 115938, 2022 04 01.
Article
em En
| MEDLINE
| ID: mdl-35219639
ABSTRACT
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 CdCl2 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 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) and specificity protein 1 (Sp1) in vivo and vitro. Furthermore, Sp1-siRNA alone reduced 11ß-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 11ß-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.
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Base de dados:
MEDLINE
Assunto principal:
Placenta
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11-beta-Hidroxiesteroide Desidrogenase Tipo 2
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article