Thymoquinone alleviates the adverse effects of cyclophosphamide on oogenesis and in vitro fertilization (IVF) in NMRI mice

Etebari, Sima; Rouki, Vajihe; Asouri, Mohsen; Nasirikenari, Mehrab; Meshkani, Seyed Elyas; Momtaz, Mohammad Reza; Amoueian, Sakineh; Babaki, Yahya; Hajati, Fateme; Ahmadi, Ali Asghar

doi:10.22038/ajp.2025.25734

Thymoquinone alleviates the adverse effects of cyclophosphamide on oogenesis and in vitro fertilization (IVF) in NMRI mice

Articles in Press

Document Type : Original Research Article

Authors

¹ Department of Physiology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

² Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

³ Clinical Department, Amol Campus of Medicine, Mazandaran University of Medical Science, Sari, Iran

⁴ North Research Center, Pasteur Institute of Iran, Amol, Iran

⁵ Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

⁶ Pathology Department-Imam Reza Hospital-Mashhad University of Sciences-Iran

⁷ Mahdiyeh Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

10.22038/ajp.2025.25734

Abstract

Objective: Patients undergoing treatment with antineoplastic drugs face numerous challenges. This study investigates the effects of thymoquinone (Tq) in NMRI mice treated with cyclophosphamide (Cph), aiming to enhance patients' optimism for the future by redirecting their focus towards achieving a normal life and restoring fertility after treatment.
Materials and Methods: Female NMRI mice were divided into five groups: Control, Sham, Cph-treated (CPH), and two groups treated with Tq alongside Cph (TQ5 and TQ10). All mice were sacrificed to aspirate their oocytes for further analysis. The development of embryos up to the blastocyst stage was assessed using in vitro fertilization (IVF) with mature oocytes.
Results: The Tq treatment groups exhibited a dose-dependent decrease in oocyte degeneration compared to the CPH group. A dose-dependent reduction in the rate of metaphase I maturation arrest was also observed in the TQ groups compared to CPH. Tq significantly increased the number of two-cell and four-cell embryos at 24- and 48-hrs post-fertilization compared to the CPH group. Additionally, Tq treatment resulted in significant dose-dependent increases in catalase levels, while malondialdehyde and nitric oxide levels were significantly lower in the TQ groups compared to the CPH groups. Tq-treated groups also demonstrated significant dose-dependent increases in the expression levels of BMP15 and GDF9 compared to the CPH group.
Conclusion: In this study, Tq mitigated oocyte factors expression (GDF9 and BMP15) and oxidative damage in ovarian tissues following CPH-induced oocyte degeneration in mice.

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