Peng Dianyi, Feng Fuqing, Yin Heng, Zhao Jianfei, Cao Shanchuan, Liu Jingbo
College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China.
Nutrients. 2025 Sep 20;17(18):3007. doi: 10.3390/nu17183007.
: Manganese (Mn) is a trace element essential for multiple physiological and biological processes. The testis plays a key role in male reproduction by producing sperm and synthesizing male hormones. This study investigates how Mn deficiency affects testicular development, spermatogenesis, and the blood-testis barrier (BTB), and evaluates associated variations in oxidative stress to explore potential mechanisms. : A Mn-deficient diet was used to induce Mn deficiency in mice, with MnCl administered via intraperitoneal injection. Mn levels in testicular tissue were measured by atomic absorption spectrometry. Testis and sperm morphology were assessed by H.E. and sperm staining. BTB markers were analyzed using immunofluorescence, Western blot, and qPCR. Oxidative stress was evaluated biochemically. Nrf2 pathway changes were detected by qPCR and Western blot. : The results indicated that Mn deficiency dramatically decreased the testicular index, caused abnormal testicular tissue structure, and significantly decreased Johnsen's score. At the same time, sperm density and motility were significantly reduced, and the sperm deformity rate was significantly increased. In addition, the BTB function was impaired, as indicated by the significantly down-regulated expression of tight junction proteins including , , , and . As the oxidative stress levels increased, the mRNA and protein expression levels of molecules (including and ) related to the Nrf2 signaling pathway were significantly down-regulated, while its inhibitor exhibited significantly up-regulated expression. Notably, after supplementing MnCl, all the above abnormal indicators were significantly improved. : Mn deficiency can lead to testicular tissue damage, decreased sperm quality, and BTB dysfunction, and the potential mechanism is probably closely associated with the increase in the oxidative stress level mediated by the Nrf2 pathway.
锰（Mn）是多种生理和生物学过程所必需的微量元素。睾丸通过产生精子和合成雄性激素在男性生殖中发挥关键作用。本研究调查锰缺乏如何影响睾丸发育、精子发生和血睾屏障（BTB），并评估氧化应激的相关变化以探索潜在机制。
采用缺锰饮食诱导小鼠锰缺乏，通过腹腔注射给予氯化锰。用原子吸收光谱法测量睾丸组织中的锰水平。通过苏木精-伊红（H.E.）染色和精子染色评估睾丸和精子形态。使用免疫荧光、蛋白质免疫印迹和定量聚合酶链反应（qPCR）分析BTB标志物。通过生化方法评估氧化应激。通过qPCR和蛋白质免疫印迹检测核因子E2相关因子2（Nrf2）途径的变化。
结果表明，锰缺乏显著降低睾丸指数，导致睾丸组织结构异常，并显著降低约翰森评分。同时，精子密度和活力显著降低，精子畸形率显著增加。此外，BTB功能受损，包括闭合蛋白、咬合蛋白、紧密连接蛋白1和紧密连接蛋白4在内的紧密连接蛋白表达显著下调。随着氧化应激水平升高，与Nrf2信号通路相关的分子（包括核因子E2相关因子2和血红素加氧酶1）的mRNA和蛋白质表达水平显著下调，而其抑制剂Keap1的表达显著上调。值得注意的是，补充氯化锰后，上述所有异常指标均得到显著改善。
锰缺乏可导致睾丸组织损伤、精子质量下降和BTB功能障碍，其潜在机制可能与Nrf2途径介导的氧化应激水平升高密切相关。
