Abstract
Pregnant women and fetuses are vulnerable to chemicals, and some reports said that chemicals exposure increases the risk of miscarriage and premature birth. The healthy fetal growth needs the proper development of placenta through syncytialization. Thus, functional and structural abnormalities in the placenta caused by chemicals could lead to adverse pregnancy outcomes, and there is a need for reproductive and developmental toxicity evaluation focusing on the placenta. However, there is still a paucity of research evaluating reproductive and developmental toxicity caused by chemicals from the perspective of placental function. Here, we selected Valproic acid (VPA) and Fluorouracil (5-FU) as model chemicals, which have been reported to induce birth defects in ICH-S5 and evaluated the effects on the syncytialization process. Human choriocarcinoma cell line (BeWo) was treated with forskolin, an inducer of syncytialization, and each chemical for 48 hours, and cell morphology was assessed by immunofluorescence and expression levels of the marker CGB and its upstream factor ERVFRD-1 by real-time RT-PCR. VPA suppressed the elevation of syncytialization rate and CGB and ERVFRD-1 expression in forskolin only treated group, suggesting that VPA inhibited syncytialization in BeWo. Although 5-FU did not change the syncytialization ratio, gene expression was enhanced compared to forskolin only treated group, indicating that 5-FU may cause placental dysfunction. Now, we try to clarify the mechanism of syncytial abnormalities by comprehensively analyzing the expression-variable molecules.
