Mechanisms of transport and toxicity of methylmercury in placental syncytiotrophoblasts

Abstract

Methylmercury (MeHg) is a prevalent environmental toxicant that is present in biological systems as a conjugate of thiol-containing molecules, such as cysteine (Cys). MeHg-Cys is a transportable form of methylmercury that can cross the placenta and cause developmental delays and defects in the fetus. However, the mechanisms by which MeHg crosses the placenta are not well characterized. The purpose of the current project was to characterize the mechanisms by which methylmercury is taken up into placental syncytiotrophoblasts and evaluate the toxicity of MeHg on these cells. BeWo cells, a placental syncytiotrophoblast line, were exposed to MeHg-Cys under various conditions and the transport of MeHg-Cys was characterized. Moreover, the toxicity of MeHg-Cys was assessed using the following biochemical assays: TBARS to measure lipid peroxidation, flow cytometry to measure mitochondrial membrane potential and cell viability, Ellman�s assay to measure thiol content within the cell, and autophagy to measure the amount of autophagosomes present. Our findings from the transport studies also show that there are sodium-independent and sodium-dependent transporters involved in the uptake of methylmercury-cysteine into BeWo cells. Potential transport proteins are System L and System B0,+, which are both sodium- independent mechanisms. Exposure to MeHg-Cys was found to be toxic to placental syncytiotrophoblasts. We found that lipid peroxidation and expression of superoxide dismutase increased, and mitochondrial membrane potential decreased, indicating a decrease in viability. The results of this study provide important insight into the mechanisms of MeHg-Cys transport and toxicity in placental syncytiotrophoblasts.