Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats

Gene. 2015 Apr 25;561(1):107-14. doi: 10.1016/j.gene.2015.02.015. Epub 2015 Feb 11.


The present study was designed to investigate whether spermatogonial stem cells (SSCs) have possible effect on doxorubicin (DOX)-induced testicular apoptosis and damaged oxidant/antioxidant balance in rats. Sixty male Albino rats were divided into 3 groups: the saline control group, the testicular toxicity group (2mg/kg DOX once a week for 8 weeks) and the third group is a donor stem cells transplanted following pre-treatment with DOX. After the 8th week, the rats were sacrificed and tissues were collected and examined for CD95, CD95L, Caspase 3, and Caspase 8 gene expression using RT-PCR. While malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) were determined using colorimetric kits. Biochemical, histopathological and PCR results showed improvement of the SSCs' group compared to the DOX-group. It was observed that spermatogonial stem cell affected DOX-induced activation of intrinsic apoptotic signaling pathway via preventing DOX-induced increases in CD95 and CD95L levels as well as cleaved Caspase-8 and Caspase-3 levels in testicular tissues, however, spermatogonial stem cell decreased Dox-induced NF-κB activation as well. It can be concluded that SSCs may be utilized to develop new cell-based therapies, and to advance germline gene therapy.

Keywords: Doxorubicin; Real-time PCR; SSCs; Testicular toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / transplantation*
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / toxicity*
  • Apoptosis / drug effects*
  • Caspase 3 / biosynthesis
  • Caspase 8 / biosynthesis
  • Catalase / metabolism
  • Cell- and Tissue-Based Therapy / methods*
  • Doxorubicin / pharmacology
  • Doxorubicin / toxicity*
  • Enzyme Activation
  • Fas Ligand Protein / biosynthesis
  • Gene Expression
  • Glutathione Peroxidase / metabolism
  • Male
  • Malondialdehyde / metabolism
  • NF-kappa B / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Rats
  • Seminiferous Tubules / physiology
  • Signal Transduction
  • Sperm Count
  • Sperm Motility
  • Sperm Retrieval
  • Spermatozoa / physiology
  • Superoxide Dismutase / metabolism
  • Testis / drug effects
  • fas Receptor / biosynthesis


  • Antibiotics, Antineoplastic
  • Fas Ligand Protein
  • NF-kappa B
  • fas Receptor
  • Malondialdehyde
  • Doxorubicin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Caspase 3
  • Caspase 8