Dimethyl Sulfoxide Attenuates Radiation-Induced Testicular Injury through Facilitating DNA Double-Strand Break Repair

Abstract

The testis is susceptible to ionizing radiation, and male infertility and sexual dysfunction are prevalent problems after whole-body or local radiation exposure. Currently, there is no approved agent for the prevention or treatment of radiation-induced testicular injury. Herein, we investigated the radioprotective effect of dimethyl sulfoxide (DMSO), an organosulfur compound that acts as a free radical scavenger, on testicular injury. Treatment of mice with a single dose of DMSO prior to 5 Gy irradiation restored sex hormones and attenuated the reduction in testis weight. Histological analyses revealed that DMSO alleviated the distorted architecture of seminiferous tubules and promoted seminiferous epithelium regeneration following irradiation. Moreover, DMSO provided quantitative and qualitative protection for sperm and preserved spermatogenesis and fertility in male mice. Mechanistically, DMSO treatment enhanced GFRα-1+ spermatogonial stem cell and c-Kit+ spermatogonial survival and regeneration after radiation. DMSO also alleviated radiation-induced oxidative stress and suppressed radiation-induced germ cell apoptosis in vivo and in vitro. Additionally, DMSO efficiently reduced DNA damage accumulation and induced the expression of phosph-BRCA1, BRCA1, and RAD51 proteins, indicating that DMSO facilitates DNA damage repair with a bias toward homologous recombination. In summary, our findings demonstrate the radioprotective efficacy of DMSO on the male reproductive system, which warrants further studies for future application in the preservation of male fertility during conventional radiotherapy and nuclear accidents.

Down Regulation of Catsper1 Expression by Calmodulin Inhibitor (Calmidazolium): Possible Implications for Fertility

“…CMZ must be dissolved in DMSO for its administration, however, our results indicate that DMSO may impair male reproductive performance. It has been reported in the literature that DMSO acts as a free-radical scavenger against the effects of radiation and helps preserve some male fertility [ 24 ]. Possible causes of impaired male fertility could be the number of injections in testicles and cell damage, since DMSO with DNA used as a transfection agent causes marked histological changes in seminiferous tubules [ 18 ].…”

Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation

“…Dimethyl sulfoxide was also found to attenuate IR-induced injury to the male reproductive system. One of the main mechanisms was that this compound elevated the expression of phosph-BRCA1, BRCA1, and RAD51, all of which indicated enhanced DSB repair with a bias toward HR [135]. In addition to BRCA1, 53BP1 is another typical protein related to methylation.…”

Autologous Cord Blood vs Individualized Supplements in Autistic Spectrum Disease – Results of the CORDUS Study

“…Besides being a vital cryoprotectant DMSO also has a multitude of actions at cellular and molecular level: acts as antioxidant (13,14), prevents accumulation of DNA breakage and facilitates DNA damage repair (15)(16)(17), is neuroprotective via decreasing glutamate and NMDA activation (18), has positive actions on neurons (19), modifies the blood-brain barrier permeability, decreases thrombosis with other vascular actions (20)(21)(22)(23)(24), induces stem cell differentiation into neuronal precursors via activation of necessary intracellular pathways (25)(26)(27)(28)(29); inhibits the pro-inflammatory function of leukocytes, including TNF-alpha function (30) and has other immunomodulatory actions (31)(32)(33)(34)(35). Because of its inhibitory action on leukocytes DMSO is "washed" from the cryopreserved grafts used for hematopoietic reconstitution (in hematology-oncology transplants), however intracellular DMSO cannot be removed and its metabolites are still felt after its administration in patients' breath.…”