Melatonin is an indoleamine with crucial antioxidant properties that are used to combat inflammatory and neoplastic processes, as well as control transplants. However, the clinical applications of melatonin have not yet been fully consolidated in the literature and require in-depth analysis. Objectives: This study reviewed the literature on the antioxidant properties of melatonin in rat models. Methods: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses and used the PubMed, LILACS, and Cochrane databases, Google Scholar, and article references, irrespective of publication time. Results: Ten articles involving 485 rats were selected, and the effects of melatonin on antioxidant markers were investigated. Melatonin increased superoxide dismutase in nine studies, glutathione peroxidase in seven studies, and catalase in five studies. In contrast, melatonin reduced glutathione in three studies and malonaldehyde in seven of eight studies. Conclusion: Our findings suggest that melatonin effectively reduces oxidative stress.

Background: Although ovarian cryopreservation is an essential strategy for fertility preservation, ischemia–reperfusion injury and oxidative stress can significantly compromise graft viability after transplantation. Melatonin is a potent antioxidant capable of modulating redox homeostasis and tissue repair; however, its effects on the ovarian microenvironment after cryopreservation are not fully understood. Objective: To investigate whether melatonin supplementation during ovarian cryopreservation enhances GPx1/2-mediated antioxidant defense, preserves follicular integrity, and modulates the angiogenic balance (assessed via VEGF-A expression) after autologous ovarian transplantation in rats. Methods: Twenty-four Wistar rats were ovariectomized and divided into control (standard cryopreservation) and melatonin-treated (0.1 μM melatonin) groups. Ovaries were cryopreserved, thawed, and autotransplanted. After 30 days, the grafts were analyzed for GPx1/2 expression (immunohistochemistry), VEGF-A levels (ELISA), biochemical markers, and follicular integrity (histomorphometry) Results: The melatonin treatment significantly increased GPx1/2 expression in the corpus luteum (p = 0.002), theca interna (p = 0.007), and interstitium (p = 0.012), and reduced the number of degenerated follicles (p = 0.03). Although absolute VEGF-A levels did not differ between groups, melatonin-treated animals showed higher VEGF/FSH ratios (p = 0.0007) and VEGF/LH (p = 0.0494) ratios. Positive correlations were observed between GPx1/2 expression and VEGF-A expression. Conclusions: Melatonin increases antioxidant defenses in cryopreserved ovarian grafts through the upregulation of GPx1/2 and preservation of follicular morphology. Instead of directly increasing VEGF-A levels, melatonin appears to modulate angiogenic signaling, contributing to a more stable microenvironment for ovarian graft survival.