Effect of Kallikrein-related Peptidase KLK1 on Ameliorating Spermatogenesis Regeneration in Busulfan-induced Azoospermic Mice and Promoting Mouse Spermatogonial Stem Cell Proliferation In Vitro
Effect of Kallikrein-related Peptidase KLK1 on Ameliorating Spermatogenesis Regeneration in Busulfan-induced Azoospermic Mice and Promoting Mouse Spermatogonial Stem Cell Proliferation In Vitro
复制标题
激肽释放酶相关肽酶KLK1改善白消安诱导无精子小鼠生精再生及促进小鼠精原干细胞体外增殖的作用
DOI：
10.1016/j.urology.2018.08.025
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发表时间：
2018-12-01
期刊：
影响因子：
2.1
通讯作者：
Li, Zheng
中科院分区：
文献类型：
--
作者：
Huang, Yuhua;Zhao, Liangyu;Li, Zheng
目的探讨激肽释放酶相关肽酶KLK 1对白消安和小鼠精原干细胞诱导的无精子症小鼠的影响。在白消安治疗后8周，处死所有小鼠，收集其睾丸用于组织学评价、免疫染色和蛋白提取。结果KLK 1处理组小鼠睾丸、附睾和附睾液的组织学观察显示，KLK 1处理组小鼠睾丸生精功能明显优于对照组。免疫染色显示，从KLK 1处理的小鼠睾丸组织样本有更多的PLZF-和SCP 3-阳性细胞每个曲细精管，以及更多的PNA-阳性细胞在曲细精管。Western印迹显示KLK 1处理小鼠的PCNA表达水平高于对照小鼠。结论KLK 1可促进无精子症小鼠精子发生，KLK 1可通过激活ERK 1/2和细胞周期蛋白Cyclin A、Cyclin E促进小鼠精原干细胞增殖。本研究为无精子症的治疗提供了新的途径和新的靶点。(C)2018由Elsevier Inc.出版
OBJECTIVES To investigate the effect of kallikrein-related peptidase KLK1 on azoospermic mice induced by busulfan and mouse spermatogonial stem cell.METHODS Mice were treated with a single intraperitoneal injection of busulfan, and 4 weeks later, they received a daily intraperitoneal injection of KLK1 at different doses for another 4 weeks. Eight weeks after the busulfan treatment, all mice were sacrificed and their testes were collected for histological evaluation, immunostaining and protein extraction. In vitro, immortalized mouse spermatogonial stem cells, namely C18-4 cells, were treated with KLK1 for proliferation assays.RESULTS Histological evaluation of testes, epididymis and epididymal fluid showed that KLK1-treated mice had better spermatogenesis than the control group. Immunostaining showed that tissue samples from testes of KLK1-treated mice had more PLZF- and SCP3-positive cells per seminiferous tubule as well as more PNA-positive cells in the seminiferous tubules. Western blots revealed higher expression levels of PCNA in KLK1-treated mice than in control mice. C18-4 cells treated with KLK1 had a higher proliferation rate and higher expression levels of PCNA, Cyclin A and Cyclin E, and the level of phosphorylated ERK2 were increased after KLK1 treatment.CONCLUSION Collectively, KLK1 can improve spermatogenesis in azoospermic mice, and KLK1 can promote the proliferation of mouse spermatogonial stem cells via activating ERK1/2 and cell cycle proteins Cyclin A and Cyclin E. This study could offer novel approach and provide new targets for the treatment of azoospermia. (C) 2018 Published by Elsevier Inc.