The effect of stem cell therapy versus melatonin on the changes induced by busulfan in the testes of adult rat: histological and immunohistochemical studies

Introduction:Chemotherapy is associated with significant gonadal damage. Melatonin has been found to be a potent free radical scavenger and antioxidant. Stem cells have the capacity to generate multiple distinct cell lineages. Aim of the work: The present study aimed to compare the effect of stem cell therapy and melatonin in the amelioration of harmful changes induced by busulfan in rat testes. Materials and methods: Forty-three adult male rats were used in the present work. Animals were divided into the following groups: group I was the control group, the rats in group II received a single dose of intraperitoneal busulfan (20 mg/kg), the rats in group III rats received 0.5 ml stem cells upon an initial dose of busulfan, the animals in group IV received a single dose of intraperitoneal melatonin (10 mg/kg) for 5 days, and the rats in group V received melatonin for 5 days upon an initial dose of busulfan. The testes were stained with H E, prussian blue, and immunohistochemical stains for the detection of caspase-3-positive and proliferating cell nuclear antigen (PCNA)-positive cells. Digital image analysis was used to determine the mean number of active caspase-3- positive and PCNA-positive cells. The results were compared statistically. Results: Busulfan-treated animals showed atrophy and irregularity of the tubules. Marked depletion of germ cells was supported by an increase in the mean number of caspase-3-positive cells in the semineferous tubules. In addition, decreased proliferative capacity was observed in the present study and confirmed by a decrease in the mean number of PCNA-positive cells. Sections of the stem cell-treated group (group III) showed incomplete or partial regeneration of germ cells with an absence of elongated and rounded spermatids. Sections of the melatonin-treated group (group V) showed almost complete regeneration of germ cells with the appearance of rounded and elongated spermatids. Conclusion: It could be concluded that melatonin was more effective than stem cells in ameliorating busulfan-induced testicular damage.