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

• Published in: Biomedical Research 2020/10/16, Vol.41(5), pp.237-242
• Main Authors: NAKANE, Hironobu, HIGAKI, Katsumi, KOYAMA, Yuka, NANBA, Eiji, KAIDOH, Toshiyuki
• Format: Article
• Language: English
• Subjects: Aging; Autophagy; Carcinogenesis; Carcinogens; Complementation; Immunoblotting; Immunohistochemistry; Infertility; Microtubule-associated protein 1; Nucleotide excision repair; Nucleotides; Pathology; Phagocytosis; Skin tests; Spermatogenesis; Tubules; Tumorigenesis; Tumors; Ultraviolet radiation; Vacuoles; Xeroderma pigmentosum
• ISSN: 0388-6107; 1880-313X
• DOI: 10.2220/biomedres.41.237

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.