PDF(Pubmed)
Abstract：
Glyphosate, the active ingredient of several broad-spectrum herbicides, is widely used throughout the world, although many adverse effects are known. Among these, it has been recognized as an endocrine disruptor. This work aimed to test the effects and potential endocrine disrupting action of glyphosate on PNT1A human prostate cells, an immortalized non-tumor epithelial cell line, possessing both ERα and ERβ estrogen receptors. The results showed that glyphosate induces cytotoxicity, mitochondrial dysfunction, and rapid activation of ERα and ERβ via nuclear translocation. Molecular analysis indicated a possible involvement of apoptosis in glyphosate-induced cytotoxicology. The apoptotic process could be attributed to alterations in mitochondrial metabolism; therefore, the main parameters of mitochondrial functionality were investigated using the Seahorse analyzer. Impaired mitochondrial function was observed in glyphosate-treated cells, with reductions in ATP production, spare respiratory capacity, and proton leakage, along with increased efficiency of mitochondrial coupling. Finally, the results of immunofluorescence analysis demonstrated that glyphosate acts as an estrogen disruptor determining the nuclear translocation of both ERs. Nuclear translocation occurred independent of dose, faster than the specific hormone, and persisted throughout treatment. In conclusion, the results collected show that in non-tumor prostate cells glyphosate can cause cell death and acts as a xenoestrogen, activating estrogen receptors. The consequent alteration of hormonal functions can have negative effects on the reproductive health of exposed animals, compromising their fertility.
摘要：
草甘膦,几种广谱除草剂的活性成分，在世界各地广泛使用，尽管已知许多不利影响。其中,它被认为是一种内分泌干扰物。这项工作旨在测试草甘膦对PNT1A人前列腺细胞的影响和潜在的内分泌干扰作用，永生化非肿瘤上皮细胞系,同时具有ERα和ERβ雌激素受体。结果表明，草甘膦诱导细胞毒性，线粒体功能障碍，并通过核易位快速激活ERα和ERβ。分子分析表明凋亡可能参与草甘膦诱导的细胞毒性。凋亡过程可归因于线粒体代谢的改变；因此，使用海马分析仪研究线粒体功能的主要参数。在草甘膦处理的细胞中观察到线粒体功能受损，随着ATP产量的减少，备用呼吸能力，和质子泄漏，随着线粒体偶联效率的提高。最后,免疫荧光分析的结果表明,草甘膦作为雌激素干扰物,决定了两种ER的核易位.核易位的发生与剂量无关，比特定的激素更快，并在整个治疗过程中坚持。总之,收集的结果表明，在非肿瘤前列腺细胞中，草甘膦可以引起细胞死亡，并充当异种雌激素，激活雌激素受体。激素功能的改变会对暴露动物的生殖健康产生负面影响，损害他们的生育能力。
