Xeroderma pigmentosum (XP) involves a defect in the initial step of nucleotide excision repair (NER) and consists of eight genetic complementation groups (groups A–G and a variant). XP group A (XPA) patients have a high incidence of UV-induced skin tumors, immature testicular development, and neurological symptoms. In an earlier study, we have shown that XP group A (Xpa) gene-knockout mice (Xpa^−/− mice) were highly sensitive to UV-induced skin carcinogenesis with a defect in NER and were highly susceptibility to spontaneous tumorigenesis with impaired spermatogenesis. However, the pathology of impaired spermatogenesis in Xpa^−/− mice is unknown. To unravel the underlying pathology, we made a concerted effort using the testis of 3-month-old Xpa^−/− mice. We found many large vacuoles in the seminiferous tubules of 3-month old Xpa^−/− mice, while there were no large vacuoles in that of Xpa^+/+ mice. Immunohistochemistry of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, showed degenerating cells with intense signal of LC3 in the seminiferous tubules, and immunoblotting revealed induction of LC3-II in the 3-month-old Xpa^−/− mice. The results of the present study suggest autophagy induction as the possible mechanism underlying the impaired spermatogenesis in Xpa^−/− mice. Therefore, Xpa^−/− mice could be a useful model for investigating aging and male infertility with low expression of XPA.

色素性干皮病 (XP) 涉及核苷酸切除修复 (NER) 初始步骤的缺陷，由八个遗传互补组（A-G 组和一个变体）组成。XP组A（XPA）患者紫外线引起的皮肤肿瘤、睾丸发育不成熟和神经系统症状的发生率很高。在早期的一项研究中，我们已经表明 XP 组 A ( Xpa ) 基因敲除小鼠 ( Xpa ^-/-小鼠) 对紫外线诱导的皮肤癌发生高度敏感，具有 NER 缺陷，并且对精子发生受损的自发性肿瘤发生高度敏感. 然而，Xpa精子发生受损的病理学^-/-老鼠是未知的。为了解开潜在的病理，我们共同努力使用 3 个月大的Xpa ^-/-小鼠的睾丸。我们在 3 个月大的Xpa ^-/-小鼠的曲细精管中发现许多大液泡，而在Xpa ^+/+小鼠的曲细精管中没有大液泡。微管相关蛋白 1 轻链 3 (LC3)（一种自噬体标记物）的免疫组织化学显示，在生精小管中具有强烈 LC3 信号的退化细胞，免疫印迹显示 3 个月大的Xpa 中诱导了 LC3-II ^-/-老鼠。本研究的结果表明自噬诱导是Xpa精子发生受损的可能机制^-/-小鼠。因此，Xpa ^-/-小鼠可能是一种有用的模型，用于研究XPA低表达的衰老和男性不育症。