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

Reprod Toxicol. 2015 Nov:57:100-10. doi: 10.1016/j.reprotox.2015.05.011. Epub 2015 Jun 3.

Abstract

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 24h 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 24h. TPP and TCEP treatments for 24h 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.

Keywords: Endocrine disruption; Oxidative stress; TM3 cell; Triphenyl phosphate; Tris-(2-chloroethyl) phosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics
  • Animals
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Gene Expression / drug effects
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Male
  • Mice
  • Organophosphates / toxicity*
  • Oxidative Stress / drug effects
  • Phosphines / toxicity*
  • Phosphoproteins / genetics
  • RNA, Messenger / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, LDL / genetics
  • Scavenger Receptors, Class B / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Testosterone / metabolism

Substances

  • Organophosphates
  • Phosphines
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, GABA-A
  • Receptors, LDL
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • steroidogenic acute regulatory protein
  • tris(2-carboxyethyl)phosphine
  • Testosterone
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase
  • Catalase
  • Glutathione Peroxidase
  • Steroid 17-alpha-Hydroxylase
  • Cholesterol Side-Chain Cleavage Enzyme
  • Superoxide Dismutase
  • Glutathione Transferase
  • triphenyl phosphate