Di-2-ethylhexyl phthalate (DEHP) induces apoptosis and autophagy of mouse GC-1 spg cells

Environ Toxicol. 2020 Feb;35(2):292-299. doi: 10.1002/tox.22866. Epub 2019 Nov 1.

Abstract

As a widely used plasticizer in industry, di-2-ethylhexylphthalate (DEHP) can cause testicular toxicity, yet little is known about the potential mechanism. In this study, DEHP exposure dramatically inhibited cellviability and induced apoptosis of mouse GC-1 spg cells. Furthermore, DEHP significantly increased the levels of autophagy proteins LC3-II, Beclin1 and Atg5, as well as the ratio ofLC3-II/LC3-I. Transmission electron microscopy (TEM) further confirmed that DEHP induced autophagy of mouse GC-1 spg cells. DEHP was also shown to induceoxidative stress; while inhibition of oxidative stress with NAC could increase cell viability and inhibit DEHP-induced apoptosis and autophagy. These results suggested that DEHP induced apoptosis and autophagy of mouse GC-1 spg cells via oxidative stress. 3-MA, an inhibitor of autophagy, could rescue DEHP-induced apoptosis. In summary, DEHP induced apoptosis and autophagy of mouse GC-1 spg cells via oxidative stress, and autophagy might exert a cytotoxic effect on DEHP-induced apoptosis.

Keywords: GC-1 spg cells; apoptosis; autophagy; di-2-ethylhexyl phthalate; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Diethylhexyl Phthalate / toxicity*
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Plasticizers / toxicity*
  • Spermatogonia / drug effects*
  • Spermatogonia / ultrastructure
  • Testis / drug effects
  • Testis / pathology

Substances

  • Plasticizers
  • Diethylhexyl Phthalate