a Biochemistry Department , Affiliated Hospital of Guizhou Medical University , Guizhou , China.
b Medical Laboratory , Guizhou Medical University , Guizhou , China.
Toxicol Mech Methods. 2018 Jun;28(5):345-352. doi: 10.1080/15376516.2017.1416714. Epub 2017 Dec 28.
Melamine is a nitrogen-containing heterocyclic organic compound with a triazine skeleton, which has been widely applied in industrial and chemical fields. Previous toxicity studies of melamine mainly focused on renal toxicity and hepatic pathological changes, but its toxicity against the reproductive system has seldom been assessed. We investigated the effects of melamine on the reproductive system of male mice. Forty healthy male Kunming mice were randomly divided into a normal saline negative control group, a low-dose melamine group, a medium-dose melamine group and a high-dose melamine group (n = 10). The mice were administered for five consecutive days and killed on the 35th day after first administration. In melamine administration groups, seminiferous tubules had disordered, loose arrangement, and spermatogenic cells at all levels obviously decreased. The sperm count and motility decreased significantly, and the sperm deformity rate increased significantly. Melamine induced apoptosis of testicular spermatogenic cells. To further explore the mechanism, we detected metabolism-related enzymes sorbitol dehydrogenase (SDH) and lactate dehydrogenase (LDH) as well as oxidative stress indices superoxide dismutase (SOD) and malondialdehyde (MDA). The activities of SDH, LDH and SOD in melamine treatment groups decreased significantly, and the MDA level increased obviously. The expressions of apoptosis-related proteins Bcl-2, Bax and caspase-3 were detected by immunohistochemistry. The expression of Bcl-2 significantly increased, but those of Bax and caspase-3 significantly reduced (p < 0.05). In conclusion, melamine damaged the reproductive system of mice via the oxidative stress pathway and by inducing cell apoptosis.
三聚氰胺是一种含氮杂环有机化合物，具有三嗪骨架，广泛应用于工业和化学领域。先前对三聚氰胺的毒性研究主要集中在肾毒性和肝病理变化上，但对其生殖系统毒性的评估较少。我们研究了三聚氰胺对雄性小鼠生殖系统的影响。将 40 只健康雄性昆明小鼠随机分为生理盐水阴性对照组、低剂量三聚氰胺组、中剂量三聚氰胺组和高剂量三聚氰胺组（n=10）。小鼠连续给药 5 天，首次给药后第 35 天处死。在三聚氰胺给药组中，曲细精管排列紊乱、疏松，各级生精细胞明显减少。精子计数和活力显著下降，精子畸形率显著升高。三聚氰胺诱导睾丸生精细胞凋亡。为了进一步探讨其机制，我们检测了代谢相关酶山梨醇脱氢酶（SDH）和乳酸脱氢酶（LDH）以及氧化应激指标超氧化物歧化酶（SOD）和丙二醛（MDA）。三聚氰胺处理组的 SDH、LDH 和 SOD 活性显著降低，MDA 水平明显升高。通过免疫组织化学检测凋亡相关蛋白 Bcl-2、Bax 和 caspase-3 的表达。Bcl-2 的表达显著增加，而 Bax 和 caspase-3 的表达显著降低（p<0.05）。综上所述，三聚氰胺通过氧化应激途径和诱导细胞凋亡损伤小鼠生殖系统。
