电离辐射诱导的男性生殖系统损伤、修复机制探索:1例电离辐射损伤患者睾丸功能变化的报告

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

目的:探究电离辐射对睾丸结构和功能的影响,为辐射损伤防治提供策略。方法:本研究采用辐射剂量模拟、精液分析、激素检测、电镜、单细胞转录组测序等技术对1例辐射损伤患者进行评估、分析;并利用小鼠模型验证单细胞测序结果,探索辐射损伤的具体生物学机制及潜在的干预手段。结果:1~2 Gy电离辐射会导致精子浓度和活力下降,12个月后逐渐恢复但精子正常形态率始终偏低。多种类固醇激素的水平失衡,睾酮和硫酸脱氢表雄酮呈下降趋势,孕酮、催乳素、黄体生成素和卵泡刺激素呈升高趋势。电镜显示睾丸结构破坏,生殖细胞丢失,生精小管萎缩,精母细胞核膜凹陷,线粒体萎缩变形,线粒体嵴减少。单细胞测序提示,睾丸间质细胞和巨噬细胞在辐射损伤后出现明显功能改变,脂类相关代谢通路出现紊乱。对动物模型进行左旋肉碱给药可以改善脂质代谢障碍,部分缓解辐射造成的生殖细胞损伤。结论:电离辐射能够引起睾丸生精障碍和性激素紊乱;间质细胞和巨噬细胞在睾丸辐射损伤后出现脂代谢通路的抑制,改善脂代谢可以缓解辐射引起的生殖细胞损伤。

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.