The impact of mesenchymal stem cells on doxorubicin-induced testicular toxicity and progeny outcome of male prepubertal rats

Abstract

Background: Many therapies to treat cancer are gonadotoxic and can lead to infertility. New strategies to diminish the side effects and protective plans during and after chemotherapy are needed. Therefore, bone marrow mesenchymal stem cells (BM-MSCs) as a novel solution were investigated against doxorubicin (Dox)-induced toxicity in rat testes.

Methods: Forty male albino prepubertal rats were divided into four groups, 10 rats per each group. The first was injected intraperitoneally with saline as control. The second group was injected intravenously with a single dose of BM-MSCs (2 × 10⁶ cells). The third was injected intraperitoneally with a single dose of Dox (5 mg/kg b.wt). The fourth was injected with both Dox and BM-MSCs as previously mentioned. Rats were cohabited each separately with an untreated adult female after 8 weeks of treatment to examine Dox effects on male's fertility.

Results: BM-MSCs counteract the deleterious effects of Dox on body, testicular weight as well as sperm quality by increasing sperm concentration and reducing the rate of abnormal sperm. BM-MSCs reduced significantly the testicular oxidative stress by reducing the elevated level of malondialdehyde and increasing the antioxidant capacity. Histologically, the testicular atrophy, severe damage of spermatogenesis and the significant reduction of the diameter and germinative cell layer thickness of the seminiferous tubules caused by Dox were significantly recovered after administration of the BM-MSCs.

Conclusion: BM-MSCs have a significant role in restoring the structural efficiency of male reproductive system in rats after Dox treatment.

Keywords: bone marrow derived-mesenchymal stem cell; doxorubicin; male fertility; oxidative stress; testicular toxicity.