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Crosstalk between endoplasmic reticulum stress and mitochondrial pathway mediates cadmium-induced germ cell apoptosis

Yan-Li Ji1, Hua Wang, Xian-Feng Zhao

  • 1Department of Toxicology, Anhui Medical University, Hefei, 230032, China.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 13, 2011
PubMed

Insights

Cadmium exposure triggers endoplasmic reticulum (ER) stress, leading to testicular germ cell apoptosis. ER chemical chaperones like phenylbutyric acid (PBA) can protect against this cadmium-induced damage.

Area of Science:

  • Toxicology
  • Reproductive Biology
  • Cellular Biology

Background:

  • Cadmium (Cd) is linked to male infertility and reduced semen quality.
  • Cd exposure is known to induce testicular germ cell apoptosis in animal models.
  • The precise molecular mechanisms underlying Cd-induced germ cell apoptosis are not fully understood.

Purpose of the Study:

  • To investigate the role of endoplasmic reticulum (ER) stress in cadmium-evoked germ cell apoptosis in testes.
  • To elucidate the molecular pathways involved in Cd-induced testicular toxicity.

Main Methods:

  • Mice were injected with Cadmium Chloride (CdCl2).
  • Levels of ER stress markers, including spliced XBP-1, GRP78, CHOP, phosphorylated eIF2α, and JNK, were measured.
  • The effect of phenylbutyric acid (PBA), an ER chemical chaperone, on Cd-induced apoptosis and mitochondrial pathways was assessed.

Main Results:

  • CdCl2 injection significantly increased spliced XBP-1, GRP78, CHOP, and phosphorylated eIF2α and JNK in mouse testes.
  • Cd exposure activated the unfolded protein response (UPR) pathway in testicular cells.
  • PBA treatment attenuated Cd-induced ER stress and germ cell apoptosis.
  • PBA also reduced the release of cytochrome c from mitochondria to cytoplasm in Cd-treated testes.

Conclusions:

  • Endoplasmic reticulum (ER) stress signaling is activated by cadmium exposure in testes.
  • The unfolded protein response (UPR) pathway plays a crucial role in mediating cadmium-induced testicular germ cell apoptosis.
  • Crosstalk between ER stress and mitochondrial pathways is involved in cadmium toxicity.
  • ER chemical chaperones like PBA show potential in mitigating cadmium-induced male reproductive toxicity.

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