Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Japan.
Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Japan.
Cell Tissue Res. 2020 Jul;381(1):203-216. doi: 10.1007/s00441-020-03190-0. Epub 2020 Apr 4.
In mammals, the reproductive system and autoimmunity regulate mutual functions. Importantly, systemic autoimmune diseases are thought to cause male infertility but the underlying pathological mechanism remains unclear. In this study, the morpho-function of the testes in BXSB/MpJ-Yaa mice was analyzed as a representative mouse model for systemic autoimmune diseases to investigate the effect of excessive autoimmunity on spermatogenesis. At 12 and 24 weeks of age, BXSB/MpJ-Yaa mice showed splenomegaly and increased levels of serum autoantibodies, whereas no controls showed a similar autoimmune condition. In histological analysis, the enlarged lumen of the seminiferous tubules accompanied with scarce spermatozoa in the epididymal ducts were observed in some of the BXSB/MpJ-Yaa and BXSB/MpJ mice but not in C57BL/6N mice. Histoplanimetrical analysis revealed significantly increased residual bodies and apoptotic germ cells in the seminiferous tubules in BXSB/MpJ-Yaa testes without apparent inflammation. Notably, in stage XII of the seminiferous epithelial cycles, the apoptotic germ cell number was remarkably increased, showing a significant correlation with the indices of systemic autoimmune disease in BXSB/MpJ-Yaa mice. Furthermore, the Sertoli cell number was reduced at the early disease stage, which likely caused subsequent morphological changes in BXSB/MpJ-Yaa testes. Thus, our histological study revealed the altered morphologies of BXSB/MpJ-Yaa testes, which were not observed in controls and statistical analysis suggested the effects of an autoimmune condition on this phenotype, particularly the apoptosis of meiotic germ cells. BXSB/MpJ-Yaa mice were shown to be an efficient model to study the relationship between systemic autoimmune disease and the local reproductive system.
在哺乳动物中，生殖系统和自身免疫调节着相互的功能。重要的是，全身性自身免疫性疾病被认为会导致男性不育，但潜在的病理机制尚不清楚。在这项研究中，我们以 BXSB/MpJ-Yaa 小鼠为代表的全身性自身免疫疾病模型，分析了睾丸的形态和功能，以研究过度自身免疫对精子发生的影响。在 12 和 24 周龄时，BXSB/MpJ-Yaa 小鼠出现脾肿大和血清自身抗体水平升高，而对照组没有出现类似的自身免疫状态。在组织学分析中，在一些 BXSB/MpJ-Yaa 和 BXSB/MpJ 小鼠的附睾管中观察到精曲小管管腔扩大，精子稀少，但在 C57BL/6N 小鼠中没有观察到这种情况。组织学计量分析显示，BXSB/MpJ-Yaa 睾丸的精曲小管中残留体和凋亡的生殖细胞明显增加，没有明显的炎症。值得注意的是，在精原细胞上皮周期的 XII 期，凋亡的生殖细胞数量显著增加，与 BXSB/MpJ-Yaa 小鼠全身性自身免疫疾病的指标呈显著相关。此外，在疾病早期 Sertoli 细胞数量减少，这可能导致 BXSB/MpJ-Yaa 睾丸随后发生形态变化。因此，我们的组织学研究揭示了 BXSB/MpJ-Yaa 睾丸的改变形态，在对照组中没有观察到这种形态，统计学分析表明自身免疫状态对这种表型的影响，特别是减数分裂生殖细胞的凋亡。BXSB/MpJ-Yaa 小鼠被证明是研究全身性自身免疫疾病与局部生殖系统之间关系的有效模型。
