First Author | Nakane H | Year | 2020 |
Journal | Biomed Res | Volume | 41 |
Issue | 5 | Pages | 237-242 |
PubMed ID | 33071259 | Mgi Jnum | J:333236 |
Mgi Id | MGI:6754763 | Doi | 10.2220/biomedres.41.237 |
Citation | Nakane H, et al. (2020) Autophagy induction on impaired spermatogenesis of xeroderma pigmentosum group A gene-deficient mice. Biomed Res 41(5):237-242 |
abstractText | 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. |