Homosalate aggravates the invasion of human trophoblast cells as well as regulates intracellular signaling pathways including PI3K/AKT and MAPK pathways

Highlights: • Homosalate inhibits survival and proliferation and invasion of human trophoblasts. • Homosalate blocks AKT and MAPK signaling pathways in trophoblast cells. • Homosalate-induced oxidative stress results in disruption of mitochondrial membrane. Homosalate is an organic ultraviolet filter used in most sunscreens but has been reported to be toxic to marine organisms. The estrogenic activity of homosalate has also been reported, but its endocrine-disrupting effect remains unclear. Although homosalate has been detected in human placental tissues, its effect on the survival of human trophoblast cells needs to be investigated. Therefore, in this study, we evaluated if HTR8/SVneo, a human trophoblast cell line, treated with homosalate showed decreasing proliferative activity in a dose-dependent manner. Homosalate promoted the death of HTR8/SVneo cells with elevated lipid peroxidation and intracellular Ca²⁺ concentration. It also induced endoplasmic reticulum stress and mitochondrial morphological disturbances associated with the differentiation of human trophoblast cells. However, when the intracellular Ca²⁺ or reactive oxygen species were removed using BAPTA-AM or N-acetyl-L-cysteine (NAC), the cell proliferation suppressed by homosalate was restored. Homosalate also significantly inhibited the invasion of HTR8/SVneo cells. Furthermore, it modulated phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways, which were involved in the cross-talk between both signaling pathways in HTR8/SVneo cells. Thus, homosalate adversely affects the survival, proliferation, and invasiveness of human trophoblast cells and therefore pregnant women should practice caution while using personal care products containing homosalate.