母体镉暴露通过扰乱甲状腺激素受体信号通路损害子痫前期胎盘血管生成。
Maternal cadmium exposure impairs placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling.
机构信息
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei 230032, Anhui, China.
Department of Electrocardiogram Diagnosis, the Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei 230060, Anhui, China.
出版信息
Ecotoxicol Environ Saf. 2022 Oct 1;244:114055. doi: 10.1016/j.ecoenv.2022.114055. Epub 2022 Sep 5.
Cadmium is a ubiquitous environmental pollutant, which can increase the risk of preeclampsia. This study was designed to determine the mechanism of cadmium exposure during pregnancy impaired placental angiogenesis that was associated with the occurrence of preeclampsia. The effects of cadmium exposure on placental thyroid hormone receptor signaling were explored. JEG3 cells were treated with CdCl (20 μM) and the Dio2 inhibitor, IOP (100 μM). Cadmium levels in maternal blood and placentae were increased in preeclampsia group. Placental angiogenesis of preeclampsia was decreased with decreased expression of PLGF and VEGF and increased expression of sFlt1. Meanwhile, the expression and nuclear translocation of thyroid hormone receptor α were decreased in preeclampsia placenta, as well as the expression of Dio2, but not the expression and nuclear translocation of thyroid hormone receptor β. Furthermore, we found that cadmium exposure downregulated the expression of thyroid hormone receptor α and Dio2, but not the expression of thyroid hormone receptor β in JEG3 cells. Also, we found that cadmium exposure decreased the expression of PLGF and VEGF and increased the expression of sFlt1 in JEG3 cells. IOP pretreatment decreased the expression of PLGF and increased the expression of sFlt1. In conclusion, our results elucidated that cadmium exposure would impair placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling.
镉是一种普遍存在的环境污染物，可增加子痫前期的风险。本研究旨在确定妊娠期间镉暴露损害胎盘血管生成的机制，这与子痫前期的发生有关。探讨了镉暴露对胎盘甲状腺激素受体信号的影响。用 CdCl（20 μM）和 Dio2 抑制剂 IOP（100 μM）处理 JEG3 细胞。子痫前期组母血和胎盘镉水平升高。子痫前期胎盘血管生成减少，PLGF 和 VEGF 表达减少，sFlt1 表达增加。同时，子痫前期胎盘甲状腺激素受体α的表达和核易位减少，Dio2 的表达减少，但甲状腺激素受体β的表达和核易位不受影响。此外，我们发现镉暴露下调 JEG3 细胞中甲状腺激素受体α和 Dio2 的表达，但不影响甲状腺激素受体β的表达。此外，我们发现镉暴露降低了 JEG3 细胞中 PLGF 和 VEGF 的表达，增加了 sFlt1 的表达。IOP 预处理可降低 PLGF 的表达，增加 sFlt1 的表达。总之，我们的结果表明，镉暴露通过干扰甲状腺激素受体信号而损害子痫前期的胎盘血管生成。
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