Nitric oxide mediates disruption of human placental trophoblast invasion induced by perfluorobutane sulfonate

Abstract

Perfluorobutane sulfonate (PFBS), an emerging pollutant, is associated with disruption of placental functions and adverse birth outcomes. However, the precise mechanism of this disruption remains unclear. Extravillous trophoblasts make up the majority of cells in the placenta, and have invasive abilities, which plays a critical role in a successful pregnancy. It has been reported that inducible nitric oxide (iNOS) and nitric oxide (NO) signaling is associated with trophoblast migration and invasion. In this study, PFBS exposure was found to enhance trophoblast invasion and increase matrix metalloproteinase 9 (MMP-9) levels. Additionally, PFBS upregulated iNOS levels and stimulated NO generation. iNOS inhibitor treatment attenuated the increased invasion of trophoblasts and MMP-9 expression induced by PFBS. Extracellular signal-regulated kinase (ERK) phosphorylation was also enhanced by PFBS exposure. In the presence of an ERK pathway inhibitor, however, the increases in trophoblast invasion, the induction of NO production, iNOS expression and MMP-9 expression induced by PFBS were attenuated. Taken together, these results suggest that iNOS/NO signaling is triggered by activation of the ERK signaling pathway, and that iNOS/NO signaling mediates PFBS-induced stimulation of trophoblast invasion.