Ibrahim Dalia, Abozied Nadia, Abdel Maboud Samar, Alzamami Ahmad, Alturki Norah A, Jaremko Mariusz, Alanazi Maram Khalil, Alhuthali Hayaa M, Seddek Asmaa
The Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
The Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Front Pharmacol. 2023 Mar 22;14:1122175. doi: 10.3389/fphar.2023.1122175. eCollection 2023.
Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one technique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects. It is an antimitotic medicine that regulates cell proliferation and primarily targets quickly dividing cells, and it has been related to varying levels of infertility in humans. In the current study, we assessed the biochemical, histological, and microscopic evaluations of testicular damage following cyclophosphamide administration. Further, we have explored the potential protective impact of mesenchymal stem cell (MSCs) transplantation. The biochemical results revealed that administration of cyclophosphamide increased serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while it decreased serum concentrations of free testosterone hormone (TH), testicular follicle-stimulating hormone, luteinizing hormone, and free testosterone hormone concentrations, testicular total antioxidant capacity (TAC), and testicular activity of superoxide dismutase (SOD) enzyme. The histology and sperm examinations revealed that cyclophosphamide induced destruction to the architectures of several tissues in the testes, which drastically reduced the Johnsen score as well as the spermatogenesis process. Surprisingly, transplantation of mesenchymal stem cell after cyclophosphamide administration altered the deterioration effect of cyclophosphamide injury on the testicular tissues, as demonstrated by biochemical and histological analysis. Our results indicated alleviation of serum and testicular sex hormones, as well as testicular oxidative stress markers (total antioxidant capacity and superoxide dismutase activity), and nearly restored the normal appearance of the testicular tissues, Johnsen score, and spermatogenesis process. In conclusion, our work emphasizes the protective pharmacological use of mesenchymal stem cell to mitigate the effects of cyclophosphamide on testicular tissues that impair the spermatogenesis process following chemotherapy. These findings indicate that transferring mesenchymal stem cell to chemotherapy patients could significantly improve spermatogenesis.
癌症是一种以异常细胞增殖为特征的致命疾病。化疗是癌症治疗的一种技术。环磷酰胺（CYP）是最有效的化疗药物，但其具有严重的副作用。它是一种抗有丝分裂药物，可调节细胞增殖，主要靶向快速分裂的细胞，并且它与人类不同程度的不育有关。在本研究中，我们评估了环磷酰胺给药后睾丸损伤的生化、组织学和显微镜评估。此外，我们还探讨了间充质干细胞（MSCs）移植的潜在保护作用。生化结果显示，环磷酰胺给药会增加血清促卵泡生成素（FSH）和促黄体生成素（LH）的浓度，同时降低血清游离睾酮激素（TH）、睾丸促卵泡生成素、促黄体生成素和游离睾酮激素的浓度、睾丸总抗氧化能力（TAC）以及睾丸超氧化物歧化酶（SOD）的活性。组织学和精子检查显示，环磷酰胺会导致睾丸中多个组织的结构遭到破坏，这大幅降低了约翰森评分以及精子发生过程。令人惊讶的是，环磷酰胺给药后间充质干细胞的移植改变了环磷酰胺损伤对睾丸组织的恶化作用，生化和组织学分析表明了这一点。我们的结果表明血清和睾丸性激素以及睾丸氧化应激标志物（总抗氧化能力和超氧化物歧化酶活性）有所缓解，并且几乎恢复了睾丸组织的正常外观、约翰森评分和精子发生过程。总之，我们的工作强调了间充质干细胞在药理上的保护作用，以减轻环磷酰胺对化疗后损害精子发生过程的睾丸组织的影响。这些发现表明，将间充质干细胞移植给化疗患者可显著改善精子发生。
