Melatonin and Testicular Damage in Busulfan Treated Mice

Mirhoseini, Mehri; Saki, Ghasem; Hemadi, Masoud; Khodadadi, Ali; Asl, Javad Mohammadi

doi:10.5812/ircmj.14463

Cited by 28 publications

(26 citation statements)

References 27 publications

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“…Then, we constructed the models of spermatogenic dysfunction by busulfan. Current studies have demonstrated that busulfan treatment can markedly cause the apoptosis of germ cells and impair normal spermatogenesis 232425. In this study, our results also showed that normal spermatogenesis was gradually impaired at 4 weeks after busulfan treatment.…”

Section: Discussionsupporting

confidence: 77%

Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis

Lei

Zhou

et al. 2017

Asian J Androl

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Recent studies have reported that caspase 7 has an apoptotic and nonapoptotic function. However, the relationship between caspase 7 and spermatogenesis remains unknown. This study aimed to investigate the possible function of caspase 7 during normal and abnormal spermatogenesis. The cleaved form of caspase 7 was detected in testis tissues at different postpartum times (5–14 weeks) by qRT-PCR, Western blot and immunohistochemistry (IHC). Then, the mice models of spermatogenic dysfunction were obtained by busulfan (30 mg kg−1 to further evaluate the potential function and mechanism of caspase 7. qRT-PCR and Western blot results showed that caspase 7 expression was gradually elevated from 5 to 14 weeks, which was not connected with apoptosis. IHC results revealed that caspase 7 was mainly located in spermatogenic cells and Leydig cells. In addition, spermatogenic dysfunction induced by busulfan gradually enhanced the apoptosis and elevated the expression of caspase 3, caspase 6, and caspase 9, but decreased the expression of caspase 7 in spermatogenic cells. However, when spermatogenic cells were mostly disappeared at the fourth week after busulfan treatment, caspase 7 expression in Leydig cells was significantly increased and positively correlated with the expression of caspase 3, caspase 6, and caspase 9. Therefore, these results indicate that caspase 7 has a nonapoptic function that participates in normal spermatogenesis, but also displays apoptotic function in spermatogenic dysfunction.

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Section: Discussionsupporting

confidence: 77%

Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis

Lei

Zhou

et al. 2017

Asian J Androl

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“…They declared that although the mechanism is not clear, it acts probably by decreasing oxidative stresses. In another study, it was achieved the protective effect of melatonin in busulfan treated mice ( 28 ). Apparently, melatonin treatment produces antioxidant effect in vivo.…”

Section: Discussionmentioning

confidence: 99%

The effect of the melatonin on cryopreserved mouse testicular cells

Saki

Mirhoseini

Hemadi

et al. 2016

IJRM

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Background:After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. Objective:The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. Materials and Methods:Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 µm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity.Results:The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group.Conclusion:The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.

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“…Melatonin co‐administration increased sperm count and motility and decreased rates of abnormal sperm. In addition, busulfan increased apoptosis in germ cells and seminiferous tubules . On the other hand, melatonin co‐administration either significantly or non‐significantly decreased apoptosis in seminiferous tubules and germ cells .…”

Section: Resultsmentioning

confidence: 93%

“…Busulfan (butane‐1,4‐diyl dimethanesulfonate) is an alkylating drug and used as an alleviating management in malignant diseases, including polycythemia vera and myeloproliferative disorders . Busulfan is a very toxic chemotherapy drug, which causes side effects in multiple organs, including the reproductive system . Busulfan induced disruption in seminiferous tubules structure, degeneration in germinal cells and a significant decrease in thickness of the seminiferous tubules in the testis .…”

Section: Resultsmentioning

confidence: 99%

“…Busulfan is a very toxic chemotherapy drug, which causes side effects in multiple organs, including the reproductive system . Busulfan induced disruption in seminiferous tubules structure, degeneration in germinal cells and a significant decrease in thickness of the seminiferous tubules in the testis . Melatonin co‐administration attenuated these consequences with its protective properties.…”

Section: Resultsmentioning

confidence: 99%

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The role of melatonin on chemotherapy-induced reproductive toxicity

Haghi‐Aminjan

Asghari

Farhood

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives Reproductive malfunctions after chemotherapy still are a reason of reducing fertility and need specialized intensive care. The aim of this review was to investigate the effect of melatonin on the reproductive system under threatening with chemotherapeutic drugs. Methods To find the role of melatonin in the reproductive system during chemotherapy, a full systematic literature search was carried out based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in the electronic databases up to 17 April 2017 using search terms in the titles and abstracts. A total of 380 articles are screened according to our inclusion and exclusion criteria. Finally, 18 articles were included in this study. Key findings It has been cleared that melatonin has bilateral effects on reproductive cells. Melatonin protects normal cells via mechanisms, including decrease in oxidative stress, apoptosis, inflammation and modulating mitochondrial function, and sexual hormones. Furthermore, melatonin with antiproliferative properties and direct effects on its receptors improves reproductive injury and function during chemotherapy. On the other hand, melatonin sensitizes the effects of chemotherapeutic drugs and enhances chemotherapy-induced toxicity in cancerous cells through increasing apoptosis, oxidative stress and mitochondrial malfunction. Conclusions The study provides evidence of the bilateral role of melatonin in the reproductive system during chemotherapy.

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Melatonin and Testicular Damage in Busulfan Treated Mice

Cited by 28 publications

References 27 publications

Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis

Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis

The effect of the melatonin on cryopreserved mouse testicular cells

The role of melatonin on chemotherapy-induced reproductive toxicity

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