[Ionizing radiation-induced damage (IRD) to and repair mechanisms of the male reproductive system: Report of testicular function changes in a case of IRD].

OBJECTIVE

To investigate the impact of ionizing radiation (IR) on the structure and function of the testis and provide some strategies for the prevention and treatment of IR-induced damage (IRD).

METHODS

Using radiation dose simulation, semen analysis, hormone testing, electron microscopy and single-cell transcriptome sequencing, we assessed and analyzed a case of IRD. We established a mouse model of IRD to validate the results of single-cell sequencing, and investigated the specific biological mechanisms of IRD and potential strategies for its intervention.

RESULTS

IR at 1－2 Gy significantly reduced sperm concentration and motility, which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low. It also caused imbalanced levels of various steroid hormones, decreased testosterone and dehydroepiandrosterone sulfate, increased progesterone, prolactin, luteinizing hormone, and follicle-stimulating hormone. Electron microscopy revealed damages to the testis structure, including loss of germ cells, atrophy of the seminiferous tubules, nuclear membrane depression of the spermatocytes, mitochondrial atrophy and deformation, and reduction of mitochondrial cristae. Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD. Administration of L-carnitine to the mouse model improved lipid metabolism disorders and partially alleviated IRD to the germ cells.

CONCLUSION

Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages. Improving lipid metabolism can alleviate IRD to germ cells.