AOPPs (advanced oxidation protein products) promote apoptosis in trophoblastic cells through interference with NADPH oxidase signaling: implications for preeclampsia

Abstract

Purpose: To investigate the role of placental advanced oxidation protein products (AOPPs) in the pathogenesis of preeclampsia (PE).Methods: Expression of AOPPs in human placental tissues collected from women with or without PE was examined by immunohistochemistry. The effect of AOPPs on in vitro trophoblast cell function was also examined. Specifically, we exposed trophoblastic cells to AOPPs and measured the production of human chorionic gonadotropin (hCG) as well as their invasion capacity using an in vitro Transwell invasion assay. We also investigated the effect of AOPPs on trophoblastic apoptosis and whether this effect could be mediated through interference in NADPH oxidase signaling.Results: AOPPs were expressed in placental tissues, and were significantly increased in placentas from women with PE versus normotensive controls. AOPPs also affected trophoblast cell function in vitro by significantly reducing β-HCG production and inhibiting trophoblas cell invasive capacity. Exposure to AOPPs significantly increased apoptosis in trophoblastic cells, which was mediated through the NADPH oxidase pathway.Conclusions: AOPPs expression is increased in PE placentas and exposure to AOPPs adversely affects trophoblast cell function, which may contribute to the shallow trophoblast invasion that characterizes this disorder. Additional studies are needed to investigate further to determine whether AOPPs can be used as a biomarker for PE.