Maternal cadmium exposure impairs placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling

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 CdCl2 (20 mu M) and the Dio2 inhibitor, IOP (100 mu M). 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 alpha were decreased in preeclampsia placenta, as well as the expression of Dio2, but not the expression and nuclear translocation of thyroid hormone receptor beta. Furthermore, we found that cadmium exposure downregulated the expression of thyroid hormone receptor alpha and Dio2, but not the expression of thyroid hormone receptor beta 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.

Automated summary

This study found that cadmium exposure reduces placental angiogenesis in preeclampsia by decreasing the expression of PLGF and VEGF and increasing the expression of sFlt1. Cadmium exposure also decreases the expression of thyroid hormone receptor alpha and Dio2. These results suggest that cadmium exposure impairs placental angiogenesis in preeclampsia by disturbing thyroid hormone receptor signaling.