BACKGROUND AND OBJECTIVE: Controversial effects of bisphenol A (BPA) have been reported on testicular function. These differences might reflect dissimilar exposure conditions. Dose responses to toxicants may be non-linear, e.g. U-shaped, with effects at low and at high levels of exposure and lower or inexistent effects at intermediate levels. Sertoli cells produce high levels of glutathione (GSH) as a cell defense mechanism. In this study, we addressed the question whether the exposure to different doses of BPA could influence Sertoli cell GSH synthesis and recycling. MATERIALS AND METHODS: Primary Sertoli cell cultures were exposed to various doses of BPA (0.5 nM-100 μM). Cell viability was measured as an outcome of toxic effect. GSH cell content was determined to evaluate cell response to toxicant exposure. Glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunit expression were assessed to estimate GSH synthesis, and GSH reductase (GR) expression to estimate GSH recycling. RESULTS: BPA 100 μM, but not lower doses, decreased cell viability. BPA 10 and 50 μM, but not lower doses, induced an increment in Sertoli cell GSH levels, due to a rapid upregulation of GCLC and GR and a slower upregulation of GCLM. CONCLUSIONS: High doses of BPA are deleterious for Sertoli cells. Intermediate doses do not affect Sertoli cell viability and increase cell content of GSH owing to increased GSH synthesis and recycling enzyme expression. Lower doses of BPA are not capable of eliciting a cell defense response. These observations may explain a non-linear dose response of Sertoli cells to BPA.
BACKGROUND AND OBJECTIVE: Controversial effects of bisphenol A (BPA) have been reported on testicular function. These differences might reflect dissimilar exposure conditions. Dose responses to toxicants may be non-linear, e.g. U-shaped, with effects at low and at high levels of exposure and lower or inexistent effects at intermediate levels. Sertoli cells produce high levels of glutathione (GSH) as a cell defense mechanism. In this study, we addressed the question whether the exposure to different doses of BPA could influence Sertoli cell GSH synthesis and recycling. MATERIALS AND METHODS: Primary Sertoli cell cultures were exposed to various doses of BPA (0.5 nM-100 μM). Cell viability was measured as an outcome of toxic effect. GSH cell content was determined to evaluate cell response to toxicant exposure. Glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunit expression were assessed to estimate GSH synthesis, and GSH reductase (GR) expression to estimate GSH recycling. RESULTS:BPA 100 μM, but not lower doses, decreased cell viability. BPA 10 and 50 μM, but not lower doses, induced an increment in Sertoli cell GSH levels, due to a rapid upregulation of GCLC and GR and a slower upregulation of GCLM. CONCLUSIONS: High doses of BPA are deleterious for Sertoli cells. Intermediate doses do not affect Sertoli cell viability and increase cell content of GSH owing to increased GSH synthesis and recycling enzyme expression. Lower doses of BPA are not capable of eliciting a cell defense response. These observations may explain a non-linear dose response of Sertoli cells to BPA.
Authors: Anna Z Pollack; Sunni L Mumford; Jenna R Krall; Andrea Carmichael; Victoria C Andriessen; Kurunthachalam Kannan; Enrique F Schisterman Journal: Environ Res Date: 2020-04-16 Impact factor: 6.498
Authors: Fjodor Melnikov; Dianne Botta; Collin C White; Stefanie C Schmuck; Matthew Winfough; Christopher M Schaupp; Evan P Gallagher; Bryan W Brooks; Edward Spencer Williams; Philip Coish; Paul T Anastas; Adelina Voutchkova-Kostal; Jakub Kostal; Terrance J Kavanagh Journal: Chem Res Toxicol Date: 2019-01-07 Impact factor: 3.739