Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China.
Institute of Reproductive Medicine, Medical School, Nantong University, Nantong 226019, China; School of Basic Medical Science, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
Reprod Biol. 2024 Sep;24(3):100928. doi: 10.1016/j.repbio.2024.100928. Epub 2024 Jul 30.
4-methylimidazole (4-MI), a derivative of imidazole, is a widely used component in caramel-colored food products such as soy sauce, beer and other soft drinks. The present study is aimed to investigate the effects of 4-MI on the male reproduction. The results revealed that 8 weeks of 4-MI exposure did not significantly alter the body weight and testicular weight of male mice. However, testicular morphology and computer-assisted sperm analysis showed that exposed to 4-MI caused irregular arrangement of spermatogenic cells in the testes and weakened sperm motility. Consistently, we observed the decreased fertilization ability in vivo of 4-MI-treated male mice. We further demonstrated that 4-MI disrupted the blood-testis barrier (BTB) integrity by decreasing the protein expression of BTB-related junction with permeability assay and western blot. In addition, the apoptosis of Sertoli cells (TM4) occurred in 4-MI treated mice, which might be caused by the generation of oxidative stress. Collectively, our findings document that 4-MI exposure damages the sperm mobility via disruption of BTB integrity.
4-甲基咪唑（4-MI）是咪唑的衍生物，是酱油、啤酒和其他软饮料等焦糖色食品产品中广泛使用的成分。本研究旨在探讨 4-MI 对男性生殖的影响。结果表明，4-MI 暴露 8 周不会显著改变雄性小鼠的体重和睾丸重量。然而，睾丸形态和计算机辅助精子分析显示，暴露于 4-MI 导致睾丸中精子发生细胞排列不规则，精子运动能力减弱。一致地，我们观察到 4-MI 处理的雄性小鼠体内的受精能力下降。我们进一步证明，4-MI 通过通透性测定和 Western blot 降低了与 BTB 相关的连接蛋白的表达，破坏了血睾屏障（BTB）的完整性。此外，在 4-MI 处理的小鼠中发生了支持细胞（TM4）的凋亡，这可能是由氧化应激引起的。总之，我们的研究结果表明，4-MI 通过破坏 BTB 完整性损害精子的运动能力。
