BackgroundEnvironmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials.MethodsA systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy’s effects on rodents’ testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872)ResultsOut of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains.ConclusionIn conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.
BackgroundModern societies face infertility as a global challenge. There are certain environmental conditions and disorders that damage testicular tissue and may cause male infertility. Melatonin, as a potential antioxidant, may protect testicular tissue. Therefore, we conducted this systematic review and meta-analysis to evaluate the effects of melatonin in animal models against physical, heat, and ischemic damage to the testicular tissue.MethodsPubMed, Scopus, and Web of Science were systematically searched to identify animal trials evaluating the protective effect of melatonin therapy on rodent testicular tissue when it is exposed to physical, thermal, ischemic, or hypobaric oxygen stress. Random-effect modeling was used to estimate the standardized mean difference and 95% confidence intervals based on the pooled data. Additionally, the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool was used to assess the risk of bias. The study protocol was prospectively registered in PROSPERO (CRD42022354599).ResultsA total of 41 studies were eligible for review out of 10039 records. Studies employed direct heat, cryptorchidism, varicocele, torsion-detorsion, testicular vascular occlusion, hypobaric hypoxia, ischemia-reperfusion, stress by excessive or restraint activity, spinal cord injury, and trauma to induce stress in the subjects. The histopathological characteristics of testicular tissue were generally improved in rodents by melatonin therapy. Based on the pooled data, sperm count, morphology, forward motility, viability, Johnsen’s biopsy score, testicular tissue glutathione peroxidase, and superoxide dismutase levels were higher in the melatonin treatment rodent arms. In contrast, the malondialdehyde level in testicular tissue was lower in the treatment rodent arms. The included studies suffered from a high risk of bias in most of the SYRCLE domains.ConclusionThis study concludes that melatonin therapy was associated with improved testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress in male rodents with physical, ischemic, and thermal testicular injuries. In this regard, melatonin deserves scientific investigations as a potential protective drug against rodent male infertility.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354599.
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