Gestational cadmium exposure impairs placental angiogenesis via activating GC/GR signaling
| Autor: | Wei-Bo Liu, Hua-Long Zhu, Yu-Feng Zhang, Yong-Wei Xiong, Hua Wang, Li-Min Dai, Xiao-Feng Xu, Guo-Xiang Zhou, De-Xiang Xu, Xue-Ting Shi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Angiogenesis
Health Toxicology and Mutagenesis Population Glucocorticoid receptor Environmental pollution Melatonin Andrology Downregulation and upregulation medicine GE1-350 education Placental angiogenesis Pregnancy education.field_of_study Chemistry Fetal growth restriction Public Health Environmental and Occupational Health General Medicine medicine.disease Pollution Environmental sciences TD172-193.5 Gestation Reticulum medicine.drug Cadmium |
| Zdroj: | Ecotoxicology and Environmental Safety, Vol 224, Iss, Pp 112632-(2021) |
| ISSN: | 0147-6513 |
| Popis: | 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 CdCl2 (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 CdCl2 (20 μM) 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 11β-HSD2 protein expression. Based upon the population case-control study, the levels of VEGF-A and 11β-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. |
| Databáze: | OpenAIRE |
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