Different Effects of the Anticonvulsant Drugs Phenytoin and Phenobarbital on Forskolin-Induced BeWo Syncytialization.

BACKGROUND: The placenta plays important roles in pregnancy maintenance and fetal development, and chemical-induced functional or structural abnormalities can lead to adverse pregnancy outcomes. However, information on the placental effects of chemicals remains limited. To help address this gap, this study aimed to investigate the effects of two model chemicals, phenytoin and phenobarbital, on syncytialization (the fusion of cytotrophoblasts into multinucleated syncytiotrophoblasts), a critical process in placental development, using the human choriocarcinoma cell line BeWo. METHODS: Phenytoin and phenobarbital, anticonvulsant drugs known to cause major congenital malformations, were each co-treated with forskolin, which promotes syncytialization in BeWo cells, for 48 h. RESULTS: Evaluation of cell fusion showed that phenytoin significantly suppressed forskolin-induced luciferase activity, whereas phenobarbital did not. Enzyme-linked immunosorbent assay showed that the concentration of human chorionic gonadotropin beta (hCGβ) in the cell culture supernatant was decreased in phenytoin-treated syncytialized BeWo cells but increased in phenobarbital-treated cells. Western blotting also showed a similar pattern in the hCG protein expression level. CONCLUSION: Collectively, these results indicate that phenytoin suppresses the process of syncytialization, whereas phenobarbital does not affect cell fusion and instead enhances hCG production.