Autophagy induction on impaired spermatogenesis of xeroderma pigmentosum group A gene-deficient mice.

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.