DMSO Protects Against Radiation-Induced Ovarian Injury by Preserving Mitochondrial Function and Alleviating DNA Damage.

BACKGROUND AND PURPOSE: Radiation-induced ovarian injury (RIOI) compromises the clinical utility of pelvic radiotherapy and reduces fertility in young female patients. Dimethyl sulfoxide (DMSO) exhibits antioxidant property. Hearin, we aimed to explore the protective effect and underlying mechanism of DMSO on RIOI.

MATERIALS AND

METHODS

C57BL/6J female mice were treated with DMSO prior to undergoing lower abdominal radiation. Intragenerational and transgenerational fertility were assessed by mating experiment. Ovaries were harvested to evaluate follicle count and morphology. Granulosa cells were analyzed by immunohistochemical staining of TUNEL and Ki67. An ovary explant organ culture system was established to evaluate the effect of DMSO. Fluorescent probes were employed to evaluate mitochondrial mass and function. DNA double-strand breaks were detected by immunoblotting of γ-H2AX.

RESULTS

DMSO preserved the fertility of irradiated mice and even safeguarded the reproductive capacity of their unirradiated female offspring. Histological analyses revealed that DMSO preserves the ovarian follicle reserve, including both primordial and developing follicles. Additionally, DMSO demonstrated radioprotective effects in ex vivo ovarian tissue. Moreover, DMSO reduced apoptosis and enhanced proliferation in granulosa cells. Mechanistically, DMSO alleviated radiation-induced oxidative stress and preserved mitochondrial function, as evidenced by increased mitochondrial mass, reduced oxidant levels, and enhanced mitochondrial membrane potential. Moreover, DMSO reduced the levels of DNA damage accumulation in vivo and in vitro.

CONCLUSION

Our data suggest that DMSO may offer a potential pharmacological treatment option for fertility impairment in women undergoing radiotherapy, which warrants further investigation in clinical settings.