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

• Spermatogonial stem cells decreased Dox-induced activation of testicular apoptosis.
• Spermatogonial stem cells prevented DOX-induced increases in CD95 and CD95L levels.
• Spermatogonial stem cells cleaved Caspase-8 and Caspase-3 in testicular tissues.
• Spermatogonial stem cell decreased Dox-induced NF-κB activation.

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 (2 mg/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.