State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Int J Mol Sci. 2019 Jul 30;20(15):3716. doi: 10.3390/ijms20153716.
As one of the Maillard reaction products, furosine has been widely reported in a variety of heat-processed foods, while the toxicity of furosine on the reproductive system and related mechanisms are unclear. Here, we constructed an intragastric gavage male mice model (42-day administration, 0.1/0.25/0.5 g furosine/Kg body weight per day) to investigate its effects on mice testicle index, hormones in serum, and mice sperm quality. Besides, the lipid metabonomics analysis was performed to screen out the special metabolites and relatively altered pathways in mice testicle tissue. Mice primary sertoli cells were separated from male mice testicle to validate the role of special metabolites in regulating pathways. We found that furosine affected testicle index, hormones expression level and sperm quality, as well as caused pathological damages in testicle tissue. Phosphatidylethanolamine (PE) (18:0/16:1) was upregulated by furosine both in mice testicle tissue and in primary sertoli cells, meanwhile, PE(18:0/16:1) was proved to activate Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α pathway, and as a functional protein in dairy products, lactoferrin could inhibit expression of this pathway when combined with furosine. In conclusion, for the first time we validated that furosine posed toxic effects on mice sperms and testicle tissue through upregulating PE(18:0/16:1) and activating Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α pathway.
作为美拉德反应产物之一，呋塞米已在多种热加工食品中广泛报道，而呋塞米对生殖系统的毒性及其相关机制尚不清楚。在这里，我们构建了一种胃内灌胃雄性小鼠模型（42 天给药，0.1/0.25/0.5 g 呋塞米/公斤体重/天），以研究其对小鼠睾丸指数、血清激素和小鼠精子质量的影响。此外，还进行了脂质代谢组学分析，以筛选出睾丸组织中特殊的代谢物和相对改变的途径。从小鼠睾丸中分离出小鼠初级支持细胞，以验证特殊代谢物在调节途径中的作用。我们发现呋塞米影响睾丸指数、激素表达水平和精子质量，并导致睾丸组织的病理损伤。在小鼠睾丸组织和初级支持细胞中，磷酸乙醇胺（PE）（18:0/16:1）均被呋塞米上调，同时，PE（18:0/16:1）被证明可以激活 Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α途径，而乳铁蛋白作为乳制品中的一种功能性蛋白质，当与呋塞米结合时，可以抑制该途径的表达。总之，我们首次验证了呋塞米通过上调 PE（18:0/16:1）并激活 Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α途径对小鼠精子和睾丸组织产生毒性作用。
