Abstract
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.
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Abbreviations
- ASA:
-
Anti-sperm antibody
- BTB:
-
Blood-testis barrier
- BXSB:
-
BXSB/MpJ-Yaa+
- BXSB-Yaa :
-
BXSB/MpJ-Yaa
- CB:
-
Citrate buffer
- DNA:
-
Deoxyribonucleic acid
- dsDNA:
-
Double-stranded DNA
- EAO:
-
Experimental autoimmune orchitis
- ELISA:
-
Enzyme-linked immunosorbent assay
- Foxp3:
-
Forkhead box P3
- IL:
-
Interleukin
- lpr:
-
Lymphoproliferation
- Nos:
-
Nitric oxide synthase
- PAS:
-
Periodic acid-Schiff
- RNA:
-
Ribonucleic acid
- S/B:
-
The ratio of spleen weight to body weight
- SE:
-
Standard error
- SLE:
-
Systemic lupus erythematosus
- ssDNA:
-
Single-stranded DNA
- St.:
-
Stage of seminiferous epithelial cycle
- tACE:
-
Testicular isoform of angiotensin-converting enzyme
- Tgf:
-
Transforming growth factor
- Tlr:
-
Toll-like receptor
- Tnf:
-
Tumor necrosis factor
- Yaa:
-
Y-linked autoimmune acceleration
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Acknowledgments
The research described in this paper was chosen for the Best Poster Presentation Award at the 6th Congress of Asian Association of Veterinary Anatomists in Malaysia (14–15 October 2017) and the Encouragement Award at the 161st Japanese Association of Veterinary Anatomists in Ibaraki (11–13 September 2018).
Funding
This study was supported in part by JSPS KAKENHI (grant number JP18J22455) (Ms. Otani).
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All animal experiments were approved by the Institutional Animal Care and Use Committee, Hokkaido University and the Faculty of Veterinary Medicine, Hokkaido University (approval No. 15-0079, 16-0124; approved by the Association for Assessment and Accreditation of Laboratory Animal Care International).
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Otani, Y., Ichii, O., Masum, M.A. et al. BXSB/MpJ-Yaa mouse model of systemic autoimmune disease shows increased apoptotic germ cells in stage XII of the seminiferous epithelial cycle. Cell Tissue Res 381, 203–216 (2020). https://doi.org/10.1007/s00441-020-03190-0
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DOI: https://doi.org/10.1007/s00441-020-03190-0