Protective or Therapeutic Effect of Exosomes Isolated From Mesenchymal Stem Cells on Cisplatin‐Induced Ovarian Damage
Arzu Yay, Zeynep Burcin Gonen, Kubra Tugce Kalkan, Betul Yalcın, Nur Seda Gokdemir, Gozde Ozge Onder, Ozge Cengiz Mat, Eda Koseoglu, Munevver Baran, Yusuf OzkulABSTRACT
Cisplatin (Cis), an index drug with the greatest gonadotoxic potential, affects both primordial follicles and developing follicles (pre‐antral) in vivo. Mesenchymal stem cell‐derived exosomes accelerate cell proliferation and wound healing. Exosomes have been shown to induce tissue regeneration by transferring growth factors, growth factor receptors, enzymes, cytokines, DNA, miRNA, mRNA, ncRNA, proteins, and lipids from cell to cell. In this study, in order to investigate the protective effects of exosomes obtained from umbilical cord‐derived mesenchymal stem cells against premature ovarian failure caused by Cis, in addition to histopathological methods, it was aimed to investigate the expressions of apoptosis, inflammation, and cell proliferation immunohistochemically at the protein level. For this purpose, 50 Wistar albino adult female rats were divided into five equal groups: control group, exosome (Exo) group, Cis group, Exo + Cis group, and Cis + Exo group. At the end of the study, ovarian tissues were removed. TNF‐α, IL‐1β, and IL‐6 enzyme levels were measured. AMH, HIF1‐α, NF‐κß, IL‐1β, PCNA, and VEGF proteins were evaluated by the immunohistochemistry staining method. When histomorphometric evaluations and AMH immunoreactivity results were examined, it was seen that Cis caused a decrease in the number of preantral follicles, and Exo tolerated this decrease in the Exo + Cis group. It was determined that the increase in NF‐κß immunoreactivity increased Cis' NF‐κß uptake, and Exo had an anti‐apoptotic effect. As a result, it was determined that Cis had a degenerative effect on ovarian morphology and follicle number and structure, and Exo applied before Cis had a prophylactic effect.