Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility

Dalia Ibrahim; Nadia Abozied; Samar Abdel Maboud; Ahmad Alzamami; Norah A Alturki; Mariusz Jaremko; Maram Khalil Alanazi; Hayaa M Alhuthali; Asmaa Seddek

doi:10.3389/fphar.2023.1122175

Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility

Front Pharmacol. 2023 Mar 22:14:1122175. doi: 10.3389/fphar.2023.1122175. eCollection 2023.

Authors

Dalia Ibrahim¹, Nadia Abozied², Samar Abdel Maboud³, Ahmad Alzamami⁴, Norah A Alturki⁵, Mariusz Jaremko⁶, Maram Khalil Alanazi⁷, Hayaa M Alhuthali⁸, Asmaa Seddek¹

Affiliations

¹ The Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
² The Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
³ The Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
⁴ Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, AlQuwayiyah, Saudi Arabia.
⁵ Clinical Laboratory Science Department, College of Applied Medical Science, King Saud University, Riyadh, Saudi Arabia.
⁶ Smart-Health Initiative and Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
⁷ Pharm.D, Scientific Office and Regulatory Affair Department, Dallah Pharma Company, Riyadh, Saudi Arabia.
⁸ Department of Clinical laboratory sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.

Abstract

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.

Keywords: MSCs; histopathology; infertility; oxidative stress; sperm; testicular injury.