Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Abstract

Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes.

New Insights into MeHg Accumulation in Rice (Oryza sativa L.): Evidence from Cysteine

“…81 Also, in mammals, the MeHg−Cysteine complex could be transported into BeWo cells via amino acid carriers and organic anion transporters. 82 The upregulation of Cys transporter gene AtLHT1 by amendment of Cys enhanced the accumulation of Hg by Arabidopsis. 60 The upregulation of the Cys transporter is thought to be associated with the internalization of Cys by plants as AAs or amino acidderived molecules, leading to increased uptake of MeHg− Cysteine complexes.…”

“…For example, the MeHg–Cysteine complex is a substrate for the neutral amino acid transporter LAT1, facilitating its transport across membranes . Also, in mammals, the MeHg–Cysteine complex could be transported into BeWo cells via amino acid carriers and organic anion transporters . The upregulation of Cys transporter gene AtLHT 1 by amendment of Cys enhanced the accumulation of Hg by Arabidopsis .…”

Genes Involved in DNA Repair and Mitophagy Protect Embryoid Bodies from the Toxic Effect of Methylmercury Chloride under Physioxia Conditions

“…This process often occurs in post-damage or post-stress defective mitochondria [55,89]. MeHg can alter mitochondrial function and viability, decrease mitophagy and autophagy, and increase oxidative stress [54]. PARK2 is one of the primary regulators of mitophagy [89].…”

“…In ESCs, comprehensive DNA damage repair mechanisms are responsible for preserving and maintaining their genome integrity [11]. However, another important mechanism that protects the integrity of the mitochondrial genome is the selective degradation of mitochondria by autophagy (mitophagy), which prevents the accumulation of dysfunctional mitochondria [54,55]. In the case of excessive DNA damage and repair dysfunction, the proapoptotic pathway is activated, leading to cell death and embryo mortality [56].…”