Park Do-Yong, Lee Byoung-Seok, Kim Woo-Jin, Im Wan-Jung, Han Ji-Seok, Park Heejin, Yang Mi-Jin, Cho Jae-Woo, Kim Da Hee, Han Su-Cheol, Kim Yong-Bum, Son Hwa-Young
Department of Advanced Toxicology Research, Korea Institute of Toxicology (KIT), Daejeon, Korea.
Department of Inhalation Research, Korea Institute of Toxicology (KIT), Jeongeup, Korea.
Lab Anim Res. 2018 Mar;34(1):20-29. doi: 10.5625/lar.2018.34.1.20. Epub 2018 Mar 22.
C57BL/6N mice are inbred strains widely used in biomedical research. Hence, a large amount of basic data has been accumulated. However, in the field of histopathology, spontaneous data for relatively younger mice that are used more frequently are not yet abundant, in contrast to data for older mice and their neoplastic lesions. To acquire the essential background data required by various research and toxicological assessments, 120 mice of the C57BL/6N strain (10 and 13 weeks of age) were collected from two institutions (From Korea and Japan) and subjected to histopathological analyses of the major organs (liver, spleen, kidney, thymus, heart, testis, epididymis). The results showed significantly higher incidence of sperm granulomas in the epididymides (10-56%) of these mice, compared with that in other strains or species of lab animals. Upon closer inspection, oligospermia/clear cell hyperplasia, cellular debris, and tubular vacuolation were also observed in the epididymides with sperm granulomas. Moreover, diseased organs were significantly heavier than healthy ones. Immunohistochemical staining showed a significant increase in the chromatic figures of cysteine-dependent aspartate-directed proteases-3 (caspase-3) and cleaved-poly(ADP-ribose) polymerase (c-PARP), and damages to the tubule due to spontaneous apoptosis, which may have led to the sperms leaking out of the tubule, causing the granuloma. To conclude, spontaneous sperm granuloma can occur in 10- and 13-week-old C57BL/6N mice and may thus affect the results of various studies using these mice. Therefore, sperm granuloma in epididymis needs to be carefully considered as an important factor when design the study using C57BL/6N.
C57BL/6N小鼠是广泛应用于生物医学研究的近交系。因此,已经积累了大量的基础数据。然而,在组织病理学领域,与老年小鼠及其肿瘤病变的数据相比,使用更为频繁的相对年轻小鼠的自发数据尚不丰富。为了获取各种研究和毒理学评估所需的基本背景数据,从两个机构(韩国和日本)收集了120只C57BL/6N品系的小鼠(10周龄和13周龄),并对主要器官(肝脏、脾脏、肾脏、胸腺、心脏、睾丸、附睾)进行了组织病理学分析。结果显示,与其他品系或种类的实验动物相比,这些小鼠附睾中精子肉芽肿的发生率显著更高(10 - 56%)。进一步检查发现,在有精子肉芽肿的附睾中还观察到少精子症/透明细胞增生、细胞碎片和小管空泡化。此外,患病器官明显比健康器官重。免疫组织化学染色显示,半胱氨酸天冬氨酸蛋白酶-3(caspase-3)和裂解的聚(ADP-核糖)聚合酶(c-PARP)的染色质图像显著增加,并且由于自发凋亡导致小管受损,这可能导致精子从小管中漏出,从而形成肉芽肿。总之,10周龄和13周龄的C57BL/6N小鼠可自发发生精子肉芽肿,因此可能影响使用这些小鼠进行的各种研究结果。所以,在设计使用C57BL/6N小鼠的研究时,附睾中的精子肉芽肿需要作为一个重要因素加以仔细考虑。