Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Front Endocrinol (Lausanne). 2023 Aug 28;14:1184745. doi: 10.3389/fendo.2023.1184745. eCollection 2023.
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
男性睾丸功能障碍是癌症治疗（包括化疗和放疗）的一个相当严重的并发症，部分原因是这些治疗引起的氧化应激增加。褪黑素是一种有效的抗氧化剂，可保护动物模型的睾丸免受物理和有毒化学应激物的伤害。本研究旨在系统地综述褪黑素对啮齿动物睾丸组织对抗癌应激物的保护作用。
在 Web of Science、Scopus 和 PubMed 上进行了广泛的检索，以寻找研究外源性褪黑素对暴露于抗癌化学物质和放射治疗剂的啮齿动物睾丸的保护作用的动物研究。使用 DerSimonian 和 Laird 随机效应模型，从汇总数据中估计标准化均数差和 95%置信区间。该方案已在国际前瞻性系统评价注册中心（PROSPERO：CRD42022355293）进行了前瞻性注册。
荟萃分析纳入了 38 项研究，其中 43 项研究符合综述要求。大鼠和小鼠接受了放射治疗（电离辐射，如伽马射线和伦琴射线和放射性碘）或化疗（甲氨蝶呤、紫杉醇、白消安、顺铂、多柔比星、长春碱、博来霉素、环磷酰胺、依托泊苷、紫杉醇、丙卡巴肼、多西他赛、和苯丁酸氮芥）。根据我们的荟萃分析，褪黑素治疗显著改善了所有结局，包括精子数量和质量（计数、活力、活力、正常形态、精原细胞数量、约翰森睾丸活检评分、生精小管直径和生精上皮高度）、血清生殖激素水平（卵泡刺激素和睾酮）、组织氧化应激标志物（睾丸组织丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶、谷胱甘肽、半胱天冬酶-3 和总抗氧化能力）和体重相关特征（体重、附睾、睾丸和相对睾丸体重）。纳入研究中的大多数 SYRCLE 领域存在高偏倚风险。此外，还检测到显著的异质性和小样本效应。
在雄性啮齿动物中，褪黑素治疗与改善睾丸组织病理学、生殖激素、睾丸和体重以及降低睾丸组织中氧化标志物水平有关。建议进行更细致的未来研究，为人类应用提供强有力的科学依据。
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293，标识符 CRD42022355293。
