Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Biol Reprod. 2021 Dec 20;105(6):1510-1520. doi: 10.1093/biolre/ioab187.
High-mobility group box 2, a chromatin-associated protein that interacts with deoxyribonucleic acid, is implicated in multiple biological processes, including gene transcription, replication, and repair. High-mobility group box 2 is expressed in several tissues, including the testis; however, its functional role is largely unknown. Here, we elucidated the role of high-mobility group box 2 in spermatogenesis. Paraffin-embedded testicular tissues were obtained from 8-week-old and 1-year-old wild-type and knock-out mice. Testis weight and number of seminiferous tubules were decreased, whereas atrophic tubules were increased in high-mobility group box 2-depleted mice. Immunohistochemistry revealed that atrophic tubules contained Sertoli cells, but not germ cells. Moreover, decreased cell proliferation and increased apoptosis were demonstrated in high-mobility group box 2-depleted mouse testis. To elucidate the cause of tubule atrophy, we examined the expression of androgen and estrogen receptors, and the results indicated aberrant expression of androgen receptor and estrogen receptor alpha in Sertoli and Leydig cells. Southwestern histochemistry detected decreased estrogen response element-binding sites in high-mobility group box 2-depleted mouse testis. High-mobility group box 1, which has highly similar structure and function as high-mobility group box 2, was examined by immunohistochemistry and western blotting, which indicated increased expression in testis. These findings indicate a compensatory increase in high-mobility group box 1 expression in high-mobility group box 2 knock-out mouse testis. In summary, depletion of high-mobility group box 2 induced aberrant expression of androgen receptor and estrogen receptor alpha, leading to decreased germ cell proliferation and increased apoptosis which resulted in focal seminiferous tubule atrophy.
高迁移率族蛋白 2 是一种与脱氧核糖核酸相互作用的染色质相关蛋白，涉及多种生物学过程，包括基因转录、复制和修复。高迁移率族蛋白 2 在多种组织中表达，包括睾丸；然而，其功能作用在很大程度上尚不清楚。在这里，我们阐明了高迁移率族蛋白 2 在精子发生中的作用。从 8 周龄和 1 岁龄的野生型和敲除小鼠中获得石蜡包埋的睾丸组织。高迁移率族蛋白 2 耗竭小鼠的睾丸重量和生精小管数量减少，而萎缩小管增加。免疫组织化学显示萎缩小管含有支持细胞，但没有生殖细胞。此外，在高迁移率族蛋白 2 耗竭小鼠睾丸中证实了细胞增殖减少和凋亡增加。为了阐明小管萎缩的原因，我们检查了雄激素和雌激素受体的表达，结果表明雄激素受体和雌激素受体α在支持细胞和间质细胞中的表达异常。西南印迹法检测到高迁移率族蛋白 2 耗竭小鼠睾丸中雌激素反应元件结合位点减少。高迁移率族蛋白 1 的结构和功能与高迁移率族蛋白 2 高度相似，通过免疫组织化学和蛋白质印迹法进行了检查，结果表明睾丸中表达增加。这些发现表明高迁移率族蛋白 2 敲除小鼠睾丸中高迁移率族蛋白 1 表达代偿性增加。总之，高迁移率族蛋白 2 的耗竭导致雄激素受体和雌激素受体α的异常表达，导致生殖细胞增殖减少和凋亡增加，导致局灶性生精小管萎缩。
