Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
Chemosphere. 2021 Dec;285:131512. doi: 10.1016/j.chemosphere.2021.131512. Epub 2021 Jul 10.
Decabromodiphenyl ether (BDE-209), an extensively used flame retardant, exists widely in the environment. Although male reproductive toxicity induced by BDE-209 has been reported, its mechanisms remain unclear. To explore the role of glycolipid metabolism in male reproductive toxicity and the potential mechanisms, forty male SD rats were divided into four groups and given gavage with BDE-209 at 0, 5, 50, and 500 mg/kg/d for 28 days. In vitro, the spermatogenic cell lines GC-2spd cells were divided into four groups: the control group, 32 μg/mL BDE-209 group, 32 μg/mL BDE-209 + 0.4 μM Fatostatin (the inhibitor of SREBP-1) group, and 0.4 μM Fatostatin group. Our results showed that BDE-209 decreased sperm quality and quantity, which was correlated with glycolipid metabolism dysbiosis of testis. The levels of glucose, triglyceride, and total cholesterol were negatively correlated with sperm concentration, and triglyceride and total cholesterol levels were negatively correlated with sperm motility, while positively correlated with the sperm malformation rate. Moreover, BDE-209 exposure activated the glycolipid metabolism pathways (PPARγ/RXRα/SCAP/SREBP-1) and mitochondrial apoptotic pathway, thereby inducing the apoptosis of spermatogenic cells. In vitro, BDE-209 caused triglyceride and total cholesterol disorder and apoptosis of GC-2spd cells, the lipid metabolism pathways inhibitor fatostain downregulated the elevation of triglyceride and total cholesterol concentrations, and suppressed apoptosis and the activation of the mitochondrial apoptotic pathway in GC-2spd cells caused by BDE-209. Our results indicated that BDE-209 induced male reproductive toxicity by causing glycolipid metabolism dysbiosis of testis resulting in activating of the mitochondrial apoptotic pathway in spermatogenic cells. The study provides new insight into the mechanisms of male reproductive toxicity caused by BDE-209.
十溴二苯醚（BDE-209）作为一种广泛使用的阻燃剂，广泛存在于环境中。虽然已有报道称 BDE-209 具有雄性生殖毒性，但具体机制尚不清楚。为了探讨糖脂代谢在雄性生殖毒性中的作用及其潜在机制，将 40 只雄性 SD 大鼠随机分为 4 组，分别给予 0、5、50 和 500mg/kg/d 的 BDE-209 灌胃 28 天。体外，将生精细胞系 GC-2spd 细胞分为 4 组：对照组、32μg/mL BDE-209 组、32μg/mL BDE-209+0.4μM Fatostatin（SREBP-1 抑制剂）组和 0.4μM Fatostatin 组。结果表明，BDE-209 降低了精子质量和数量，这与睾丸糖脂代谢失调有关。葡萄糖、甘油三酯和总胆固醇水平与精子浓度呈负相关，甘油三酯和总胆固醇水平与精子活力呈负相关，与精子畸形率呈正相关。此外，BDE-209 暴露激活了糖脂代谢途径（PPARγ/RXRα/SCAP/SREBP-1）和线粒体凋亡途径，从而诱导生精细胞凋亡。体外，BDE-209 导致 GC-2spd 细胞甘油三酯和总胆固醇紊乱和凋亡，脂质代谢途径抑制剂 Fatostain 下调了 BDE-209 引起的甘油三酯和总胆固醇浓度升高，并抑制了 GC-2spd 细胞的凋亡和线粒体凋亡途径的激活。研究结果表明，BDE-209 通过引起睾丸糖脂代谢失调，激活生精细胞中线粒体凋亡途径，导致雄性生殖毒性。该研究为 BDE-209 引起雄性生殖毒性的机制提供了新的见解。
