Immediate intratesticular injection of circulating blood serum-derived exosomes may alleviate orchitis caused by cisplatin

• Published in: Reproductive and developmental medicine Vol. 9; no. 2; pp. 75 - 82
• Main Authors: Khani Hemmatabadi, Fuzieh, Partovyan, Marya, Chavoshinezhad, Negin, Keivan, Mona, Dadfar, Reza, Moradi Maryamneghari, Shima, Mansouri Torghabeh, Fatemeh
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.06.2025
• Subjects: Circulating blood serum-derived exosome; Inflammation; Intratesticular; Mice; Orchitis; Cisplatin
• ISSN: 2096-2924; 2589-8728
• DOI: 10.1097/RD9.0000000000000103

Objective: Cisplatin (CIS), as a common chemotherapy drug, induces detrimental effects on the testis. Besides, exosomes represent various beneficial effects, such as anti-inflammation and proliferation. In this experimental study, the authors aimed to evaluate the anti-inflammatory effects of circulating blood serum-derived exosomes on orchitis caused by CIS exposure. Methods: Male mice (n = 18) were categorized into three main groups: control (no treatment), CIS (mice with orchitis caused by CIS injection), and CIS + exosome (orchitis-induced animals followed by exosome treatment). Exosomes were extracted from circulating blood, and orchitis was induced by intraperitoneal injection of CIS (7.5 mg/kg/day) for five consequence days. A day after the last dose of CIS, the exosome (10 IU/20 g mice) was injected intratesticularly. After a week, the samples, including blood serum and testis, were gathered. The levels of oxidative stress were assessed using malondialdehyde (MDA) and nitric oxide (NO) assays. Sperm parameters (morphology, viability, motility, and count), testosterone levels, and inflammatory (tumor necrosis factor-α [TNF-α], interleukin (IL)-6, and IL-10) gene expression were also evaluated. Histopathological and testicular apoptotic index (AI) were evaluated using hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings, respectively. Finally, data analysis was applied by SPSS (v.19) software, and P <0.05 was considered as a significant level. Results: Following CIS administration, the sperm indices and testosterone levels were decreased (P <0.05); besides, NO, MDA, AI, and inflammatory gene expression were increased (P <0.05) in the CIS group compared to control animals. Following the prescription of exosomes in CIS animals, the sperm indices and testosterone levels were increased (P <0.05), and NO, MDA, AI, and inflammatory genes were decreased (P <0.05). Histopathological assessments also revealed disruption of seminiferous tubules and free from sperms following CIS administration. Also, the histological structure of damaged seminiferous tubules was changed to normal status following Exoxome prescription in CIS-exposure animals. Conclusion: Immediate intratesticular injection of blood-derived exosomes can alleviate orchitis CIS-exposed animals through anti-inflammatory features.