Prolonged melatonin treatment promote testicular recovery by enhancing RAC1-mediated apoptotic cell clearance and cell junction-dependent spermatogensis after heat stress

Guo, Yao; Chen, Hui; Wang, Qiangjun; Qi, Xin; Li, Qin; Fu, Wei; Huang, Jie; Chen, Yao; Liu, Zhongying; Wang, Meizhi; An, Liguo; Tian, Jianhui; Z, Wu

doi:10.1016/j.theriogenology.2020.12.015

Cited by 16 publications

(10 citation statements)

References 64 publications

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“…These reports are supported by the present finding that displayed testicular antioxidant improvements, including MLT, and decreased oxidative stress with MLT treatment after irradiation. These findings are congruent with previous reports after IR and heat stressed testis [39,40], which might clarify the MLT's ability to preserve the Sertoli cell tight-junction [41,42], of which the destruction was suggested to cause spermatogenic disruption and thus, male infertility [43].…”

Section: Discussionsupporting

confidence: 92%

Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties

et al. 2022

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Background Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. Methods Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. Results Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2′-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. Conclusions These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.

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Section: Discussionsupporting

confidence: 92%

Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties

et al. 2022

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“…To ensure the distribution of Oxa within the entire colon, mice were held in a vertical position for 5 min after the injection. For melatonin treatment, mice were administered 50 mg/kg of melatonin (experimental group) or solvent (control group) daily (via gavage) for 1 week before induction of colitis according to published articles ( 37 – 39 ). Melatonin was purchased from MedChemExpress (CAS Number: 73-31-4) and dissolved in dimethyl sulfoxide (DMSO).…”

Section: Methodsmentioning

confidence: 99%

Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner

et al. 2022

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Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.

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“…Endogenously elevated melatonin levels were relevant to decrease apoptosis of the Leydig cell, increase testosterone production, and improve sperm quality in melatonin-enriched transgenic mammals ( Yang et al, 2021 ). It can reduce oxidative stress and endoplasmic reticulum stress of mouse spermatocytes induced by heat stress, promote DSB repair of spermatocytes, and reduce apoptosis of spermatocytes ( Guo et al, 2020 ). After melatonin administration in varicocele rat models, MDA level in testis decreased, antioxidant enzyme activity increased, and bax expression and NO levels decreased ( Onur et al, 2004 ).…”

Section: Experimental Antioxidant Therapy With Varicocelementioning

confidence: 99%

Role of Oxidative Stress in Varicocele

et al. 2022

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According to the official statistics of the World Health Organization, at least 48 million couples and 186 million people suffer from infertility. Varicocele has been recognized as the leading cause of male infertility and can affect spermatogenesis and cause testicular and epididymal disorders through multiple diverse pathophysiological processes. Reactive oxygen species (ROS) produced by oxidative stress have been reconciled as an important pathogenic factor throughout the course of varicocele. Testis respond to heat stress, hypoxia, and inflammation at the cost of producing excessive ROS. High levels of ROS can lead to infertility not only through lipid peroxidation or DNA damage, but also by inactivating enzymes and proteins in spermatogenesis. This review studies the oxidative stress and its role in the pathophysiology and molecular biology of varicocele in the context of a decline in fertility.

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Prolonged melatonin treatment promote testicular recovery by enhancing RAC1-mediated apoptotic cell clearance and cell junction-dependent spermatogensis after heat stress

Cited by 16 publications

References 64 publications

Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties

Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties

Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner

Role of Oxidative Stress in Varicocele

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