Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells

Environ Toxicol. 2017 Mar;32(3):1055-1064. doi: 10.1002/tox.22304. Epub 2016 Jul 14.

Abstract

Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 μM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 μM) and glutathione peroxidase (GSH-Px) activity (50 and 100 μM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1055-1064, 2017.

Keywords: Di(2-ethylhexyl) phthalate (DEHP); GC-2spd cells; apoptosis; mitochondrial pathway; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cells, Cultured
  • Diethylhexyl Phthalate / toxicity*
  • Endocrine Disruptors / toxicity*
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Plasticizers / toxicity
  • Signal Transduction / drug effects
  • Spermatocytes / drug effects*
  • Spermatocytes / metabolism

Substances

  • Endocrine Disruptors
  • Plasticizers
  • Diethylhexyl Phthalate
  • Caspase 3
  • Caspase 9