Cisplatin-induced azoospermia and testicular damage ameliorated by adipose-derived mesenchymal stem cells

Abstract

Background The testes are highly susceptible to the adverse effects of chemotherapy and radiation at all stages of life. Exposure to these threats mainly occurs during cancer treatment and as an occupational hazard in radiation centers. The present study investigated the regenerative ability of adipose-derived mesenchymal stem cells (ADMSCs) against the adverse effects of cisplatin on the structure and function of the testes. Methods New Zealand white rabbits (N = 15) were divided into three groups of five: a negative control group (no treatment), a cisplatin group (single dose of cisplatin into each testis followed three days later by a PBS injection), and a cisplatin + ADMSCs group (cisplatin injection followed three days later by an ADMSC injection). On day 45 post-treatment, serum testosterone levels were evaluated, and the testes and epididymis were collected for histology, oxidative stress examination, and epididymal sperm analysis. Results Cisplatin caused damage to the testicular tissue and decreased serum testosterone levels, epididymal sperm counts, and oxidants. An antioxidant imbalance was detected due to increasing malondialdehyde (MDA) and reduced glutathione (GSH) levels in testicular tissue. The ADMSC-treated group displayed a moderate epididymal sperm count, adequate antioxidant protection, suitable hormone levels, and enhanced testicular tissue morphology. Conclusions ADMSCs treatment repaired damaged testicular tissue, enhanced biochemical parameters, and modified pathological changes caused by cisplatin.

Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression

“…The present study revealed that CIS increases the immunohistochemical expression of spermatogenic cells for Bax and decreases them for PCNA, indicating an increase of apoptosis and a decrease of the proliferation processes of spermatogenic cells, which coincide with others. , The reduced proliferation of spermatogenic cells in the present study may be owing to the CIS causing low testosterone levels, which in turn causes reduction of spermatogenesis; however, the increased apoptosis may be owing to the excess of ROS production and translocation of Bax from the cytoplasm to the perinuclear site …”

“…In parallel, cisplatin treatment caused a decrease in the level of serum testosterone. Testosterone promotes protein synthesis in all spermatogenic cells, so it plays a significant role in the formation of sperm . Moreover, cisplatin lowered the immune/inflammatory status and stimulated apoptosis and oxidative stress biomarkers .…”

Combined laser-activated SVF and PRP remodeled spinal sclerosis via activation of Olig-2, MBP, and neurotrophic factors and inhibition of BAX and GFAP

“…The process was repeated for 3 successive passages. Once the desired number of cells was achieved, the cells were cryopreserved in liquid nitrogen 34 .…”

Roles of adipose-derived stem cells and derived exosomes in therapeutic applications to testicular injury caused by cisplatin

“…The digestion was stopped by adding a culture medium, and the cell suspension was collected and centrifuged at 1000 rpm for 3 minutes. The supernatant was discarded, and the cell pellet was resuspended in PBS and centrifuged again before being analyzed by flow cytometry [ 13 ].…”

“…The animal model of testicular cell damage was established by intraperitoneal injection of a 10mg/kg cisplatin solution. Three days after modeling, the testicular cell damage model + cell therapy group received a tail vein injection of 3*10^6 CM-DiI-labeled ADSCs cells, while the testicular cell damage model + Ex group received a tail vein injection of 100μg of ADSC-Ex The normal control group and the testicular cell damage model group received an equal volume of saline via tail vein injection [13][14][15]. The procedures of Dil labeling were as follow: remove the supernatant from the culture dish and replace it with serumfree basal medium dulbecco's modified eagle medium/nutrient mixture F-12 (DMEM/F12) for cell cultivation.…”