Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies

Abstract

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.

Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies

“…In the current meta-analysis, melatonin restored testicular injuries caused by radiotherapy and chemotherapy, which was indicated by increased spermatogonia and sperm count, normal morphology, motility, and viability, testis and epididymal weight, and seminiferous tubular height and diameter. These results agree with our previous meta-analyses, which revealed the beneficial impact of melatonin on testicular injuries induced by metabolic disorders, physical and toxic chemical triggers in animal models ( 70 – 72 ). Radio- and chemotherapy can cause disturbances in spermatogenesis through different mechanisms.…”

“…Melatonin administration elevated animal testosterone and reduced FSH levels in this meta-analysis. According to our recent meta-analysis, melatonin increases testosterone levels but does not affect FSH in rodents with toxin-induced testicular injuries ( 70 ). The existing body of research suggests that melatonin can inhibit the biosynthesis of FSH by decreasing the secretion of gonadotropin-releasing hormone (GnRH).…”

Melatonin increased antioxidant capacity to ameliorate growth retardation and intestinal epithelial barrier dysfunction in diquat‐challenged piglets

“…Melatonin can not only directly clear hydroxyl radical and peroxyhydroxyl radical in vitro and vivo, but also increase antioxidant enzyme activity, such as SOD and GSH‐Px, through MT1 and MT2 receptors to reduce oxidative stress levels 27,28 . A previous study has reported that melatonin alleviated growth retardation induced by deoxynivalenol, nicotine, and ochratoxin A 29‐31 . Consistent with the previous study, our study showed that dietary supplementation with 2 mg kg −1 melatonin significantly increased ADG and feed conversion rate, and melatonin also relieved diquat‐caused weight loss, which indicated that dietary supplementation with 2 mg kg −1 melatonin may be also an effective way to alleviate diquat‐induced growth retardation in piglets.…”

“…27,28 A previous study has reported that melatonin alleviated growth retardation induced by deoxynivalenol, nicotine, and ochratoxin A. [29][30][31] Consistent with the previous study, our study showed that dietary supplementation with 2 mg kg −1 melatonin significantly increased ADG and feed conversion rate, and melatonin also relieved diquat-caused weight loss, which indicated that dietary supplementation with 2 mg kg −1 melatonin may be also an effective way to alleviate diquat-induced growth retardation in piglets. Intestinal epithelial barrier function is the key to maintaining intestinal homeostasis.…”

Effect of nutraceutical supplementation on semen quality in stallions

“…These results agree with studies on Shetland ponies (Deichsel et al., 2008) and Andalusian stallions (Ruiz et al., 2021). Other studies have observed an increase in the percentage of abnormal sperm in conditions of hypoxia, where the predominant anomalies are head malformations, unlike tail anomalies that are more frequent in normal conditions (Dehdari et al., 2023). Exogenous antioxidants function as electron donors, avoiding an oxide‐reduction chain sacrificing their own molecular integrity, through three levels of protection: Prevention: consists of the formation of ROS above normal levels of the organism.…”