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Antioxidants
Volume 15
Issue 5
10.3390/antiox15050551
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Article

Melatonin Enhances Glutathione Peroxidase Activity and Improves Antioxidant Defense in Cryopreserved Ovarian Transplants: A Rat Model Study

by
Karla Krislane Alves Costa Monteiro
1,*,
Luciana Lamarão Damous
1,
Marcos Eiji Shiroma
1,
José Antonio Orellana Turri
1,
Ricardo dos Santos Simões
1,
Manuel de Jesus Simões
1,
José Cipolla-Neto
2,
Lara Termini
3,
Rinaldo Florencio-Silva
4,
Peter Chedraui
1,5,
Russel J. Reiter
6,
Edmund Chada Baracat
1 and
Jose Maria Soares Junior
1
1
Laboratório de Ginecologia Estrutural e Molecular (LIM-58), Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas HC-FMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, Brazil
2
Laboratório de Neurobiologia Pineal, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil
3
Laboratório de Inovação em Câncer, Centro de Pesquisa Translacional em Oncologia (CTO), Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-000, Brazil
4
Department of Morphology and Genetics/Discipline of Histology and Structural Biology, Escola Paulista de Medicina—Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo 04023-062, Brazil
5
Escuela de Postgrado en Salud, Universidad Espíritu Santo, Samborondón 092301, Ecuador
6
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2026, 15(5), 551; https://doi.org/10.3390/antiox15050551
Submission received: 25 February 2026 / Revised: 20 April 2026 / Accepted: 21 April 2026 / Published: 26 April 2026
(This article belongs to the Topic Redox Modulation, Antioxidants, and Metabolites in Animals Through the One Health Concept)
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Abstract

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.
Keywords: cryopreservation; fertility preservation; GPx; VEGF; ovarian transplantation; oxidative stress; angiogenesis; rats cryopreservation; fertility preservation; GPx; VEGF; ovarian transplantation; oxidative stress; angiogenesis; rats

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MDPI and ACS Style

Monteiro, K.K.A.C.; Damous, L.L.; Shiroma, M.E.; Turri, J.A.O.; Simões, R.d.S.; Simões, M.d.J.; Cipolla-Neto, J.; Termini, L.; Florencio-Silva, R.; Chedraui, P.; et al. Melatonin Enhances Glutathione Peroxidase Activity and Improves Antioxidant Defense in Cryopreserved Ovarian Transplants: A Rat Model Study. Antioxidants 2026, 15, 551. https://doi.org/10.3390/antiox15050551

AMA Style

Monteiro KKAC, Damous LL, Shiroma ME, Turri JAO, Simões RdS, Simões MdJ, Cipolla-Neto J, Termini L, Florencio-Silva R, Chedraui P, et al. Melatonin Enhances Glutathione Peroxidase Activity and Improves Antioxidant Defense in Cryopreserved Ovarian Transplants: A Rat Model Study. Antioxidants. 2026; 15(5):551. https://doi.org/10.3390/antiox15050551

Chicago/Turabian Style

Monteiro, Karla Krislane Alves Costa, Luciana Lamarão Damous, Marcos Eiji Shiroma, José Antonio Orellana Turri, Ricardo dos Santos Simões, Manuel de Jesus Simões, José Cipolla-Neto, Lara Termini, Rinaldo Florencio-Silva, Peter Chedraui, and et al. 2026. "Melatonin Enhances Glutathione Peroxidase Activity and Improves Antioxidant Defense in Cryopreserved Ovarian Transplants: A Rat Model Study" Antioxidants 15, no. 5: 551. https://doi.org/10.3390/antiox15050551

APA Style

Monteiro, K. K. A. C., Damous, L. L., Shiroma, M. E., Turri, J. A. O., Simões, R. d. S., Simões, M. d. J., Cipolla-Neto, J., Termini, L., Florencio-Silva, R., Chedraui, P., Reiter, R. J., Baracat, E. C., & Soares Junior, J. M. (2026). Melatonin Enhances Glutathione Peroxidase Activity and Improves Antioxidant Defense in Cryopreserved Ovarian Transplants: A Rat Model Study. Antioxidants, 15(5), 551. https://doi.org/10.3390/antiox15050551

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