TPP and TCEP induce oxidative stress and alter steroidogenesis in TM3 Leydig cells

• The toxicity of TPP and TCEP on TM3 Leydig cells were studied.
• TPP and TCEP decreased the cell viability and changed the cell morphology.
• TPP and TCEP increased the SOD, CAT, GPX, GST activities and their mRNA levels.
• TPP and TCEP decreased T synthesis related genes expression and T levels.

Effects of triphenyl phosphate (TPP) and tris-(2-chloroethyl) phosphate (TCEP) exposure on induction of oxidative stress and endocrine disruption were investigated in TM3 cells. After 24 h exposure, cell growth declined and morphology changed in TPP and TCEP treated groups with high dosages. Significant increases in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST) activities and their respective gene expressions in a dose-dependent and/or time-dependent manner in TPP or TCEP groups. Moreover, the expression of main genes related to testosterone (T) synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) were dramatically reduced by TPP and TCEP treatments, especially with the high dosage for 24 h. TPP and TCEP treatments for 24 h caused significant decreases in T levels in the medium. Furthermore, co-treatments of hCG with TPP or TCEP could inhibit hCG-induced changes in the expression of P450scc, P450-17α and 17β-HSD and T levels. Taken together, TPP and TCEP could induce oxidative stress and endocrine disruption in TM3 cells.