Song Jingyu, Gao Xintao, Tang Zhe, Li Hao, Ruan Yajun, Liu Zhuo, Wang Tao, Wang Shaogang, Liu Jihong, Jiang Hongyang
Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
Andrology. 2020 May;8(3):793-806. doi: 10.1111/andr.12764. Epub 2020 Feb 16.
Diabetes mellitus (DM) induces impairment of male reproductive system and is considered as a key factor that could partially provide an explanation for male infertility. Thus, understanding the mechanism underlying DM-induced infertility will aid in the identification of novel therapeutic stratagems.
To delineate the role of ROS/JAK2/NFκB pathway in DM-induced low reproductive function and impaired spermatogenesis. Additionally, to investigate the protective effect of monomeric Berberine (BB) that inhibits ROS/JAK2/NFκB pathway, in the pathogenesis of DM-induced infertility.
12-week-old male Sprague-Dawley rats were divided into four groups: control group, DM group, control plus BB group, and DM plus BB group. Streptozotocin was used to induce DM. After treating the rats with BB for 4 weeks, fertility tests were conducted to investigate the reproductive function, and testis weight along with sperm motility was assessed through microscope. Oxidative stress was evaluated by DHE staining. TUNEL staining was utilized to detect the state of apoptosis. Cell experiments were carried out to define the role of BB in vitro. Immunohistochemistry, immunofluorescence, and Western blotting were employed to measure the protein expression.
Our results indicate that the reproductive function of DM rats was low, accompanied by decreased testis weight and sperm motility in addition to the impairment of the seminiferous tubules. However, there was a significant improvement in the reproductive function parameters in the BB-treated DM rats. Subsequently, our data revealed that DM rats produce an increased level of ROS in the testis, which activates JAK2 further activating the NFκB pathway, leading to increased apoptosis and impaired cells in the testicles. However, BB could attenuate the ROS production and abrogate activation of JAK2/NFκB pathway, thus inhibiting the apoptosis in the testicular cells of DM rats.
ROS/JAK2/NFκB pathway is involved in the DM-induced low reproductive function and impaired spermatogenesis. BB can play a protective role in preserving the reproductive function and spermatogenesis in DM by inhibiting ROS/JAK2/NFκB pathway.
糖尿病（DM）会导致男性生殖系统功能受损，被认为是部分解释男性不育的关键因素。因此，了解糖尿病导致不育的潜在机制将有助于确定新的治疗策略。
阐述活性氧（ROS）/Janus激酶2（JAK2）/核因子κB（NFκB）信号通路在糖尿病诱导的生殖功能低下和精子发生受损中的作用。此外，研究抑制ROS/JAK2/NFκB信号通路的小檗碱单体（BB）在糖尿病诱导的不育发病机制中的保护作用。
将12周龄雄性Sprague-Dawley大鼠分为四组：对照组、糖尿病组、对照加BB组和糖尿病加BB组。使用链脲佐菌素诱导糖尿病。用BB处理大鼠4周后，进行生育力测试以研究生殖功能，并通过显微镜评估睾丸重量和精子活力。通过二氢乙啶（DHE）染色评估氧化应激。采用末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色检测细胞凋亡状态。进行细胞实验以确定BB在体外的作用。采用免疫组织化学、免疫荧光和蛋白质印迹法检测蛋白质表达。
我们的结果表明，糖尿病大鼠的生殖功能低下，伴有睾丸重量和精子活力下降以及生精小管受损。然而，用BB治疗的糖尿病大鼠的生殖功能参数有显著改善。随后，我们的数据显示，糖尿病大鼠睾丸中的ROS水平升高，激活JAK2，进一步激活NFκB信号通路，导致睾丸细胞凋亡增加和细胞受损。然而，BB可以减少ROS的产生并消除JAK2/NFκB信号通路的激活，从而抑制糖尿病大鼠睾丸细胞的凋亡。
ROS/JAK2/NFκB信号通路参与了糖尿病诱导的生殖功能低下和精子发生受损。BB通过抑制ROS/JAK2/NFκB信号通路，在保护糖尿病患者的生殖功能和精子发生方面发挥保护作用。
