Depletion of high-mobility group box 2 causes seminiferous tubule atrophy via aberrant expression of androgen and estrogen receptors in mouse testis†
Depletion of high-mobility group box 2 causes seminiferous tubule atrophy via aberrant expression of androgen and estrogen receptors in mouse testis†
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DOI：
10.1093/biolre/ioab187
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发表时间：
2021-10-30
影响因子：
3.6
通讯作者：
Hishikawa, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sugita, Naohiro;Choijookhuu, Narantsog;Hishikawa, Yoshitaka
高迁移率组盒 2 是一种与脱氧核糖核酸相互作用的染色质相关蛋白，参与多种生物过程，包括基因转录、复制和修复。高迁移率组盒 2 在多种组织中表达，包括睾丸；然而，其功能作用很大程度上未知。在这里，我们阐明了高迁移率族盒 2 在精子发生中的作用。石蜡包埋的睾丸组织取自8周龄和1岁的野生型和敲除小鼠。在高迁移率组 Box 2 耗尽的小鼠中，睾丸重量和生精小管数量减少，而萎缩性小管增加。免疫组织化学显示，萎缩的肾小管含有支持细胞，但不含生殖细胞。此外，在高迁移率 Group Box 2 缺失的小鼠睾丸中，细胞增殖减少，细胞凋亡增加。为了阐明肾小管萎缩的原因，我们检测了雄激素和雌激素受体的表达，结果表明支持细胞和间质细胞中雄激素受体和雌激素受体α表达异常。 Southwestern 组织化学检测到高迁移率组盒 2 耗尽的小鼠睾丸中雌激素反应元件结合位点减少。高迁移率组框1与高迁移率组框2具有高度相似的结构和功能，通过免疫组织化学和蛋白质印迹检查表明在睾丸中表达增加。这些发现表明高迁移率组框 2 敲除小鼠睾丸中高迁移率组框 1 表达出现代偿性增加。总之，高迁移率组盒2的缺失诱导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细胞凋亡增加，导致局灶性生精小管萎缩。高迁移率组盒2的缺失诱导雄激素受体和雌激素受体α异常表达，导致生殖细胞增殖减少和细胞凋亡增加，导致生精小管萎缩。
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.Depletion of High-mobility group box 2 induced aberrant androgen receptor and estrogen receptor alpha expression, leading to decreased germ cell proliferation and increased apoptosis, resulting in seminiferous tubule atrophy.