Abstract
The placenta is responsible for delivering oxygen and nutrients to the fetus and is a very important organ in sustaining pregnancy. Placenta is formed when cellular trophoblasts (CTs) differentiate into extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STs). The adverse effects on the mother and the child are enormous. Therefore, there is a great need to establish an evaluation system for predicting toxicity to placental development. However, the placental structure varies widely among species and is difficult to evaluate in experimental animals. We are aiming to establish an evaluation system for placental toxicity using cell lines established from human placentas and blastocysts. Cadmium is known to be associated not only with renal toxicity but also with placental toxicity. Using CT27 trophoblast stem cells, we investigated the effects of cadmium exposure on placentation by evaluating the expression of various differentiation markers by qPCR, and found that cadmium has an inhibitory effect on syncytialization. However, a few μM was required for the inhibition of syncytial formation. On the other hand, differentiation into EVT-like cells was inhibited at concentrations between 100 and 400 nM. In other words, it was clear that EVT differentiation was affected by lower concentrations of Cd. The effects of cadmium on the migration and invasion ability of EVT were also observed using HTR-8/SVneo EVT-like cells. The migration and invasion of HTR-8/SVneo cells were inhibited even when exposed to concentrations as low as 20 nM. These results suggests that cadmium might cause placental dysfunction by inhibiting EVT differentiation and function, thereby increasing the risk of early preterm. In this symposium, I will present results of placental toxicity evaluation using these cell lines.
