4-Methylbenzylidene-camphor inhibits proliferation and induces reactive oxygen species-mediated apoptosis of human trophoblast cells.

4-Methylbenzylidene-camphor (4-MBC) is an estrogenic compound used in a variety of personal care products and is associated with water pollution. In this study, we verified that exposure to 4-MBC suppresses the proliferation and invasiveness of the HTR8/SVneo human trophoblast cell line. Moreover, HTR8/SVneo cells treated with 4-MBC underwent apoptosis with increased DNA fragmentation. 4-MBC also activated the PI3K/AKT and ERK1/2 signaling pathways in HTR8/SVneo cells. Furthermore, 4-MBC induced oxidative stress mediated by reactive oxygen species production, which was associated with HTR8/SVneo cell death. 4-MBC promoted lipid peroxidation and loss of mitochondrial membrane potential in HTR8/SVneo cells and activated the expression of genes encoding a protein expressed on the surface of human trophoblast cells, including the EPH receptor B4 and G protein-coupled receptor 56 genes. Therefore, 4-MBC may retard the normal growth and survival of human trophoblast cells and may hamper normal placental formation during early pregnancy.