Zhang Jianhai, Zhang Yufang, Liang Chen, Wang Nasui, Zheng Heping, Wang Jundong
Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China; Veterinary Station in Chen Villages of Lin Country, Linxian, Shanxi 033200, China.
Toxicol Appl Pharmacol. 2016 Nov 1;310:205-214. doi: 10.1016/j.taap.2016.09.018. Epub 2016 Sep 20.
Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration.
已知氟化物会导致雄性生殖毒性，对其潜在机制的阐明是生殖毒理学和流行病学领域正在进行的研究重点。胆碱是一种必需营养素，人们对其在神经系统中的益处进行了广泛研究，但很少讨论其对雄性生殖系统的潜在影响。本研究旨在探讨胆碱通过丝裂原活化蛋白激酶（MAPK）途径对氟化钠诱导的雄性生殖毒性的潜在保护作用。从母鼠妊娠到产后15周，分别给雄性小鼠饮用含150mg/L氟化钠的水、在饮食中添加5.75g/kg胆碱以及两者的组合。结果表明，氟暴露会降低体重增长、降低精子数量和存活率、改变睾丸组织学、下调睾丸中神经生长因子（NGF）、Ras、Raf和丝裂原活化蛋白激酶激酶（MEK）基因的mRNA表达，以及显著降低睾丸中NGF和磷酸化MEK蛋白的表达。对胆碱处理小鼠的数据检查显示，补充胆碱改善了这些由氟引起的变化。综上所述，我们的研究结果表明，补充胆碱可通过恢复NGF和磷酸化MEK的表达来减轻氟诱导的睾丸毒性。胆碱的合适剂量和补充时期有待进一步探索。
