Neuroendocrine and epigenetic effects of methylmercury and thimerosal on the SH-SY5Y neuroblastoma cell line under testosterone and estradiol modulation

Abstract Humans are frequently exposed to organic forms of mercury, particularly methylmercury and ethylmercury. These compounds exert toxic effects on the central nervous system. Neurodevelopmental disorders show sex-related differences, and such effects may be influenced by sex hormones like testosterone and estradiol. This study investigated the neurotoxic effects of thimerosal and methylmercury on SH-SY5Y human neuroblastoma cells under hormone-modulated conditions by measuring serotonin, serotonin transporter protein (SERT), dopamine, and dopamine transporter protein (DAT) levels and determining epigenetic alterations. Study groups (n = 3) were: control; T: thiomersal (1.15 μM); M: methylmercury (2.93 μM); testosterone-dominant environment+thimerosal group [TT: testosterone (1 μM) + estradiol (0.75 μM) + thimerosal (1.15 μM)]; estradiol-dominant environment+thimerosal group [ET: estradiol (7.5 μM) + testosterone (0.1 μM) + thimerosal (1.15 μM)]; testosterone-dominant environment+methylmercury group [TM: testosterone (1 μM) + estradiol (0.75 μM) + methylmercury (2.93 μM)] and estradiol-dominant environment+methylmercury group [EM: estradiol (7.5 μM) + testosterone (0.1 μM) + methylmercury (2.93 μM)]. Dopamine levels significantly increased in methylmercury- and thimerosal-treated cells under testosterone-modulated conditions. Elevated serotonin and SERT levels were observed in the methylmercury-treated group. Both compounds enhanced histone H3 acetylation, while hormone modulation produced distinct epigenetic responses. These findings suggest that testosterone and estradiol can modify the neurotoxic and epigenetic effects of thimerosal and methylmercury in human neuronal cells.