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.

Backgroud: Melatonin has anti-inflammatory and antioxidative actions at the mitochondrial level. This indole-containing molecule may protect ovarian grafts during the process of cryopreservation. Therefore, we aimed to determine whether melatonin pretreatment improves rat ovarian graft quality. Methods: Twenty-six female rats were allocated to two study groups of thirteen animals each: 1) control group: ovaries cryopreserved using the standard protocol; and 2) melatonin group: ovaries cryopreserved in a medium with melatonin. Ten rats of each group were submitted to 24-h freezing, and whole ovaries autologous and avascular transplantation with retroperitoneal placement. After postoperative (PO) day 15, daily vaginal smears were obtained for estrous cycle characterization. Between PO days 30 and 35, the animals were euthanized and ovarian grafts were recovered for histological and immunohistochemical (Ki-67, cleaved caspase-3, TUNEL, von Willebrand factor, estrogen, and progesterone receptors) analyses. The ovaries of the three remaining rats from each group were studied immediately after thawing to assess the effects of cryopreservation. ANOVA and Tukey’s tests were used and the rejection level of the null hypothesis was set at 0.05 or 5% (p < 0.05). Results: Melatonin promoted faster restart of the estrous cycle and increased the expression of mature follicles, collagen type I, von Willebrand factor, Ki-67, and cleaved caspase-3 on corpora lutea and estrogen receptors in the ovaries as compared to control. There was a reduction in apoptosis by TUNEL on follicles, corpora lutea, and collagen type III. Conclusion: Based on the evaluated parameters, melatonin may promote the quality of ovarian grafts. Reproductive function enhancement should be further studied.

Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms ‘melatonin’ AND ‘ovary’ AND ‘transplantation.’ After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin’s antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting.

The use of secretome may be a new strand of cell therapy, which is equal to or even superior to the injection of live cells, called cell-free therapy. In ovarian transplantation, this approach may be a therapeutic possibility for the ovarian graft in hypoxia. We designed the present study to evaluate whether the cell-free therapy with the secretome of adipose tissue-derived stem cells (ASCs) in rat frozen-thawed ovarian grafts could protect a graft against ischemic injury. A single dose of rat ASCs secretome or vehicle was injected into the bilateral frozen-thawed ovaries of 18 adult female rats immediately after an autologous transplant. Nine animals were used to control the cryopreservation protocol and were evaluated before and after the cryopreservation process. Daily vaginal smears were performed for estrous cycle evaluation until euthanasia on postoperative day 30. Follicle viability by trypan blue, graft morphology by HE, and apoptosis by TUNEL and cleaved-caspase-3 were assessed. No differences were found with respect to estrous cycle resumption and follicle viability (p > 0.05). However, compared with the vehicle-treated grafts, the morphology of the secretome-treated grafts was impaired, showing reduced follicular population and increased apoptosis (p < 0.05). ASC secretome impaired the rat frozen-thawed ovarian graft from ischemic injury. However, more studies are needed to evaluate the factors involved and the possibility of applying the secretome in scaffolds to optimize its use.

Introduction: The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement ther-apy may attenuate the reduction. Objectives: This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats.Methods: Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 mu g/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solu-tion. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results: Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 +/- 0.026 mu/m2) and the early raloxifene (0.437 +/- 0.012 mu/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 +/- 0.038 mu/m2 and 0.277 +/- 0.015 mu/m2 respectively).Conclusions: The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

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.