Hostname: page-component-77c89778f8-5wvtr Total loading time: 0 Render date: 2024-07-21T18:19:34.195Z Has data issue: false hasContentIssue false
  • English
  • Français

Morphological Features of the Testis among Autoimmune Mouse Model and Healthy Strains

Published online by Cambridge University Press:  05 August 2021

Zeinab Shouman ,
Hany E. Marei ,
Ahmed Abd-Elmaksoud ,
Mohamed Kassab ,
Takashi Namba ,
Md. Abdul Masum ,
Yaser Hosny Ali Elewa Open the ORCID record for Yaser Hosny Ali Elewa [Opens in a new window] ,
Osamu Ichii Open the ORCID record for Osamu Ichii [Opens in a new window]  and
Yasuhiro Kon
Zeinab Shouman
Affiliation:
Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura35516, Egypt Laboratory of Anatomy, Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo060-0818, Japan
Hany E. Marei
Affiliation:
Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura35516, Egypt
Ahmed Abd-Elmaksoud
Affiliation:
Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura35516, Egypt
Mohamed Kassab
Affiliation:
Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafrelsheikh University, kafrelsheikh33516, Egypt
Takashi Namba
Affiliation:
Laboratory of Anatomy, Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo060-0818, Japan
Md. Abdul Masum
Affiliation:
Laboratory of Anatomy, Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo060-0818, Japan
Yaser Hosny Ali Elewa
Affiliation:
Laboratory of Anatomy, Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo060-0818, Japan Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig44519, Egypt
Osamu Ichii
Affiliation:
Laboratory of Anatomy, Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo060-0818, Japan Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, Japan
Yasuhiro Kon*
Affiliation:
Laboratory of Anatomy, Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo060-0818, Japan
*
*Corresponding author: Yasuhiro Kon, E-mail: y-kon@vetmed.hokudai.ac.jp
Get access

Abstract

Autoimmune diseases play a critical role in the progression of infertility in both sexes and their severity has been reported to increase with age. However, few reports have discussed their effect on the morphological features of the testis. Therefore, we compared the morphological alterations in the testes of autoimmune model mice (MRL/MpJ-Faslpr) and the control strain (MRL/MpJ) with those of their background strain (C57BL/6N) at 3 and 6 months. Furthermore, we analyzed the changes in spermatocytes, Sertoli cells, immune cells, and Zonula occludens-1 junctional protein by immunohistochemical staining. The MRL/MpJ-Faslpr mice showed a significant increase in the serum Anti-double stranded DNA antibody level, relative spleen weight, and seminiferous luminal area when compared with other studied two strains. In contrast, a significant decrease in the relative testis weight, and numbers of both Sertoli, meiotic spermatocyte was observed in MRL/MpJ-Faslpr and MRL/MpJ mice compared with C57BL/6N mice especially at 6 months. Similarly, Zonula occludens-1 junctional protein positive cells showed a significant decrease in the same strains at 6 months. However, no immune cell infiltration could be observed among the studied three strains. Our findings suggest that the increase in autoimmune severity especially with age could lead to infertility through loss of spermatogenic and Sertoli cells, rather than the disturbance of the blood–testis barrier.

Keywords

autoimmune diseaseimmune cellMRL/MpJ-Faslpr miceseminiferous tubulesSertoli cells
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 27 , Issue 5 , October 2021 , pp. 1209 - 1217
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of the Microscopy Society of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

Equal contribution to this article.

References

Ahmed, EA & de Rooij, DG (2009). Staging of mouse seminiferous tubule cross-sections. Methods Mol Biol 558, 263–277.CrossRefGoogle ScholarPubMed
da Silva, C, Bonfá, E, Borba, E, Braga, AP, Soares, PM, Júlia, A, Moraes, P, Saito, O & Cocuzza, M (2009). Reproductive health in male systemic lupus erythematosus. Bras J Rheumatol 49(3), 207–227.Google Scholar
Fanning, AS, Jameson, BJ, Jesaitis, LA & Anderson, JM (1998). The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273, 29745–29753.CrossRefGoogle ScholarPubMed
Goronzy, JJ & Weyand, CM (2012). Immune aging and autoimmunity. Cell Mol Life Sci 69, 1615–1623.CrossRefGoogle ScholarPubMed
Henry, T & Mohan, C (2005). Systemic lupus erythematosus–Recent clues from congenic strains. Arch Immunol Ther Exp (Warsz) 53(3), 207–212. PMID: 15995581.Google ScholarPubMed
Hewicker, M, Kromschroder, E & Trautwein, G (1990). Detection of circulating immune complexes in MRL mice with different forms of glomerulonephritis. Z Versuchstierkd 33(4), 149–156.Google ScholarPubMed
Heydemann, A (2012). The super super-healing MRL mouse strain. Front Biol (Beijing) 7(6), 522–538.CrossRefGoogle ScholarPubMed
Heyting, C (1996). Synaptonemal complexes: Structure and function. Curr Opin Cell Biol 8, 389–396.CrossRefGoogle ScholarPubMed
Jacobo, P, Guazzone, VA, Theas, MS & Lustig, L (2011). Testicular autoimmunity. Autoimmun Rev 10, 201–204.CrossRefGoogle ScholarPubMed
Johnson, L, Thompson, DL Jr & Varner, DD (2008). Role of Sertoli cell number and function on regulation of spermatogenesis. Anim Reprod Sci 105, 23–51.CrossRefGoogle ScholarPubMed
Johnson, L, Zane, RS, Petty, CS & Neaves, WB (1984). Quantification of the human Sertoli cell population: Its distribution, relation to germ cell numbers, and age-related decline. Biol Reprod 31, 758–795.CrossRefGoogle ScholarPubMed
Khizroeva, J, Nalli, C, Bitsadze, V, Lojacono, A, Zatti, S, Andreoli, L, Tincani, A, Shoenfeld, Y & Makatsariya, A (2019). Infertility in women with systemic autoimmune diseases. Best Pract Res Clin Endocrinol Metab 33(6), 101369.CrossRefGoogle ScholarPubMed
Kon, Y & Endoh, D (2000). Morphological study of metaphase-specific apoptosis in MRL mouse testis. Anat Histol Embryol 29(5), 313–319.CrossRefGoogle ScholarPubMed
Kyrönlahti, A, Euler, R, Bielinska, M, Schoeller, EL, Moley, KH, Toppari, J, Heikinheimo, M & Wilson, DB (2011). GATA4 regulates Sertoli cell function and fertility in adult male mice. Molecular Cell Endocrinol 333, 85–95.CrossRefGoogle ScholarPubMed
Lee, J, Richburg, JH, Younkin, SC & Boekelheide, K (1997). The Fas system is a key regulator of germ cell apoptosis in the testis. Endocr Soc 138, 5.Google ScholarPubMed
Meistrich, ML & Hess, RA (2013). Assessment of spermatogenesis through staging of seminiferous tubules. Methods Mol Biol 927, 299–307.CrossRefGoogle ScholarPubMed
Moreno, RD, Reyes, JG, Parada, BA, Farías, JG, Aguirre, V, Zepeda, AB, Figuero, CA, Pino, UJ & Nemoto, Y (2012) Chapter 1 - Spermatogenesis at the extreme: Oxidative stress as a converging mechanism of testicular damage due to pathological and environmental exposure. In Testis: Anatomy, Physiology and Pathology, Nemoto, Y & Inaba, N (Eds.), pp. 1–24. Nova Science Publishers.Google Scholar
Mruk, DD & Cheng, CY (2015). The mammalian blood-testis barrier: Its biology and regulation. Endocr Rev 36(5), 564–591.CrossRefGoogle ScholarPubMed
Namiki, Y, Kon, Y, Kazusa, K, Asano, A, Sasaki, N & Agui, T (2005). Quantitative trait loci analysis of heat stress resistance of spermatocytes in the MRL/mpj mouse. Mamm Genome 16(2), 96–102.CrossRefGoogle ScholarPubMed
Neto, FT, Bach, PV, Najari, BB, Li, PS & Goldstein, M (2016). Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol 59, 10–26.CrossRefGoogle ScholarPubMed
Otani, Y, Ichii, O, Masum, MA, Kimura, J, Nakamura, T, Elewa, YHA & Kon, Y (2020). 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. doi:10.1007/s0041-020-03190-0.CrossRefGoogle ScholarPubMed
Otsuka, S, Konno, A, Hashimoto, Y, Sasaki, N, Endoh, D & Kon, Y (2008). Oocytes in newborn MRL mouse testes. Biol Reprod 79(1), 9–16.CrossRefGoogle ScholarPubMed
Otsuka, S, Namiki, Y, Ichii, O, Hashimoto, Y, Sasaki, N, Endoh, D & Kon, Y (2010). Analysis of factors decreasing testis weight in MRL mice. Mamm Genome 21(3–4), 153–161.CrossRefGoogle ScholarPubMed
Perry, D, Sang, A, Yin, Y, Zheng, YY & Morel, L (2010). Murine models of systemic lupus erythematosus. J Biomed Biotechnol 2011, 271694.Google Scholar
Ray, S, Sonthalia, N, Kundu, S & Ganguly, S (2012). Autoimmune disorders: An overview of molecular and cellular basis in today's perspective. J Clin Cell Immunol S10:003, 2215–2230.Google Scholar
Riccioli, A, Salvati, L, D'Alessio, A, Starace, D, Giampietri, C, De Cesaris, P, Filippini, A & Ziparo, E (2003). The Fas system in the seminiferous epithelium and its possible extra-testicular role. Andrologia 35, 64–70.CrossRefGoogle ScholarPubMed
Sharpe, RM, McKinnell, C, Kivlin, C & Fisher, JS (2003). Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125, 769–784.CrossRefGoogle ScholarPubMed
Silva, CA, Coccuzza, M, Carvahlo, JF & Bonfá, E (2014). Diagnosis and classification of autoimmune orchitis. Autoimmun Rev 13, 431–434.CrossRefGoogle ScholarPubMed
Soares, PMF, Borba, EF, Bonfa, E, Hallak, J, Corrêa, AL & Silva, CA (2007). Gonad evaluation in male systemic lupus erythematosus. Arthritis Rheumatol 56(7), 2352–2361.CrossRefGoogle ScholarPubMed
Song, HK & Hwang, DY (2017). Use of C57BL/6n mice on the variety of immunological researches. Lab Anim Res 33(2), 119–123.CrossRefGoogle ScholarPubMed
Suehiro, RM, Borba, EF, Bonfa, E, Okay, TS, Cocuzza, M, Soares, PM & Silva, CA (2008). Testicular Sertoli cell function in male systemic lupus erythematosus. Rheumatology 47, 1692–1697.CrossRefGoogle ScholarPubMed
Takano, H & Kazuhiro, ABE (1987). Age-related histologic changes in the adult mouse testis. Arch Histol Jap 50(5), 533–544.CrossRefGoogle ScholarPubMed
Tripathi, UK, Chhillar, S, Kumaresan, A, Aslam, MK, Rajak, SK, Nayak, S, Manimaran, A, Mohanty, TK & Yadav, S (2015). Morphometric evaluation of seminiferous tubule and proportionate numerical analysis of Sertoli and spermatogenic cells indicate differences between crossbred and purebred bulls. Vet World 8, 645–650.CrossRefGoogle ScholarPubMed
Tung, KSK & Teuscher, C (1995). Mechanisms of autoimmune disease in the testis and ovary. Hum Reprod Update 1(1), 35–50.CrossRefGoogle ScholarPubMed
Wittchen, ES, Haskins, J & Stevenson, BR (1999). Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3. J Biol Chem 274, 35179–35185.CrossRefGoogle Scholar
Yuan, L, Liu, J-G, Zhao, J, Brundell, E, Daneholt, B & Höög, C (2000). The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5, 73–83.CrossRefGoogle ScholarPubMed
Supplementary material: File

Shouman et al. supplementary material

Shouman et al. supplementary material

Download Shouman et al. supplementary material(File)
File 1.5 MB