Melatonin protects spermatogonia from the stress of chemotherapy and oxidation via eliminating reactive oxidative species

Zhang, Xiaoyu; Qin, Xia; Wei, Rui; Song, Hongfei; Mi, Jiaqi; Lin, Zhaoyu; Yang, Yang; Sun, Zijie; Zou, Kang

doi:10.1016/j.freeradbiomed.2019.04.009

Cited by 44 publications

(41 citation statements)

References 52 publications

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“…As the strongest endogenous free radical scavenger of ROS and inducer of antioxidant systems in vivo (Bonnefont-Rousselot et al, 2011), melatonin is involved in various physiological processes, such as apoptosis and autophagy in cancer cells, neurodegeneration and progressions of liver diseases as well as other pathologies (Fernandez et al, 2015). Recent studies by peers and us have shown that melatonin could protect testes against heat-induced damage (Zhang et al, 2020a) and spermatogonia against the stress of chemotherapy and oxidation via elimination of ROS (Zhang et al, 2019), and that melatonin also has protective roles against Cr (VI)-induced apoptosis and the global levels of H3K9me3 and H3K27me3 in mouse SSCs (Lv et al, 2018). Nevertheless, whether melatonin has effects on Cr (VI)-induced RNA m 6 A modification in SSCs and, if any, the underlying mechanisms remain to be probed.…”

Section: Introductionmentioning

confidence: 99%

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Yang

et al. 2021

Front. Cell Dev. Biol.

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Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and any damage to SSCs may result in spermatogenic disorder and male infertility. Chromium (Cr) (VI) is a proven toxin, mutagen, and carcinogen, perpetually detrimental to environmental organisms due to its intricate and enduring detoxification process in vivo. Despite this, the deleterious effects of Cr (VI) on SSCs and the underlying mechanisms remain poorly understood. In this study, we identified that Cr (VI) impaired male reproductive system in mouse testes and induced mitochondrial dynamic imbalance and mitophagy in SSCs/progenitors. Cr (VI) also downregulated the RNA N6-methyladenosine (m6A) modification levels in mitochondrial dynamic balance and mitophagy genes in SSCs/progenitors. Inspiringly, the toxic effects of Cr (VI) could be relieved by melatonin pretreatment. Melatonin alleviated Cr (VI)-induced damage to male reproductive system and autophagy in mouse testes. Melatonin also attenuated Cr (VI)-induced cell viability loss and reactive oxygen species (ROS) generation, as well as mitochondrial dynamic disorders and mitophagy in SSCs/progenitors. The protective roles of melatonin against Cr (VI)-induced mitophagy were exerted by restoration of METTL3-mediated RNA m6A modification and activation of mitochondrial fusion proteins MFN2 and OPA1, as well as inhibition of the mitophagy BNIP3/NIX receptor pathway. Thus, our study provides novel insights into the molecular mechanisms for RNA m6A modification underlying the gene regulatory network responsible for mitochondrial dynamic balance, and also lays new experimental groundwork for treatment of Cr (VI)-induced damage to male fertility.

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Section: Introductionmentioning

confidence: 99%

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Yang

et al. 2021

Front. Cell Dev. Biol.

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“…Studies in mice revealed that melatonin alleviates busulfan-induced toxicity through ROS elimination and apoptosis inhibition of spermatogonial progenitor cells. It has been proven that mouse spermatogonial progenitor cells express melatonin receptors suggesting that melatonin can act directly on these cells [61]. In addition, other studies indicate that melatonin does not interfere with the anti-tumoral effect of busulfan and hence, it can protect fertility without affecting the outcome of the oncological treatment [62,63].…”

Section: Experimental Strategies Based On Pharmacological Protectimentioning

confidence: 99%

“…In vivo studies in mice showed that only the combination of melatonin injection prior to chemotherapy and long-term injection during treatment was able to alleviate the toxicity of busulfan. Hence, one of the main limitations of using melatonin as a fertility-protective agent is its short half-life that reduces the efficiency of the treatment [61]. Moreover, given that the exact mechanism of melatonin action has not been elucidated yet, it creates concerns about undesirable side effects and should be further investigated.…”

Section: Experimental Strategies Based On Pharmacological Protectimentioning

confidence: 99%

Oncofertility: Pharmacological Protection and Immature Testicular Tissue (ITT)-Based Strategies for Prepubertal and Adolescent Male Cancer Patients

Ntemou

Alexandri

Lybaert

et al. 2019

IJMS

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While the incidence of cancer in children and adolescents has significantly increased over the last decades, improvements made in the field of cancer therapy have led to an increased life expectancy for childhood cancer survivors. However, the gonadotoxic effect of the treatments may lead to infertility. Although semen cryopreservation represents the most efficient and safe fertility preservation method for males producing sperm, it is not feasible for prepubertal boys. The development of an effective strategy based on the pharmacological protection of the germ cells and testicular function during gonadotoxic exposure is a non-invasive preventive approach that prepubertal boys could benefit from. However, the progress in this field is slow. Currently, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells is offered to prepubertal boys as an experimental fertility preservation strategy by a number of medical centers. Several in vitro and in vivo fertility restoration approaches based on the use of ITT have been developed so far with autotransplantation of ITT appearing more promising. In this review, we discuss the pharmacological approaches for fertility protection in prepubertal and adolescent boys and the fertility restoration approaches developed on the utilization of ITT.

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“…Oxidative stress is defined as a disorder in the balance between pro-oxidant species and antioxidants, in favor of the former, which implies the generation of reactive oxygen species (O 2 , H 2 O 2 , OH − ), reactive nitroxyl species (peroxynitrite), and degradative products of lipid peroxidation (lipid peroxides, malondialdehyde, isoprostanes), which are used to measure oxidative-stress levels. Various antioxidant agents have been used with the aim of unbalancing the oxidation equilibrium, and increasing the capacity of biological systems to rapidly detoxify oxidative reactive species and prevent or repair the resulting damage [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Melatonin as an Agent for Direct Pulp-Capping Treatment

Guerrero‐Gironés

Alcaina-Lorente

Ortiz-Ruiz

et al. 2020

IJERPH

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Melatonin plays an essential role in the regulation of bone growth. The actions that melatonin exerts on odontoblasts may be similar to its action on osteoblasts. This research aimed to evaluate the pulp response to melatonin used for direct pulp capping to evaluate the antioxidant effect of melatonin administered orally and its influence on dental pulp. Direct pulp capping was performed on the upper molars of Sprague Dawley rats using melatonin or Mineral Trioxide Aggregate (MTA). The study groups were: MTA; Melatonin; MTA + Melatonin administered orally; and Melatonin + Melatonin administered orally. In the latter two groups, the animals drank water dosed with melatonin ad libitum (10 mg/100 mL). After 30 days, the animals were sacrificed, and 5 ml of blood, the kidneys, and the liver were extracted in order to evaluate oxidative stress using thiobarbituric acid reactive substances testing (TBARS). Fragments of the maxilla containing the study molars were prepared for histological evaluation. The degree of pulp inflammation and pulp necrosis, the presence of reparative dentin and dentin bridging the pulp chamber, the presence and regularity of the odontoblastic layer, and the presence of pulp fibrosis were evaluated. No significant differences were found between the four study groups for any of the studied histological variables. The oral administration of melatonin did not modify the local effects of MTA or melatonin on dental pulp, or reduce basal-level oxidative stress. The effect of melatonin on pulp is similar to that of MTA and may be used as an agent for direct pulp capping.

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Melatonin protects spermatogonia from the stress of chemotherapy and oxidation via eliminating reactive oxidative species

Cited by 44 publications

References 52 publications

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Oncofertility: Pharmacological Protection and Immature Testicular Tissue (ITT)-Based Strategies for Prepubertal and Adolescent Male Cancer Patients

Melatonin as an Agent for Direct Pulp-Capping Treatment

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