Abstract：
Environmental exposure to endocrine disruptors, such as pesticides, could contribute to a decline of human fertility. Glyphosate (GLY) is the main component of Glyphosate Based Herbicides (GBHs), which are the most commonly herbicides used in the world. Various animal model studies demonstrated its reprotoxicity. In Europe, GLY authorization in agriculture has been extended until 2034. Meanwhile the toxicity of GLY in humans is still in debate. The aims of our study were firstly to analyse the concentration of GLY and its main metabolite, amino-methyl-phosphonic acid (AMPA) by LC/MS-MS in the seminal and blood plasma in an infertile French men population (n=128). We secondly determined Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) using commercial colorimetric kits and some oxidative stress biomarkers including malondialdehyde (MDA) and 8-hydroxy-2\'-deoxyguanosine (8-OHdG) by ELISA assays. We next analysed potential correlations between GLY and oxidative stress biomarkers concentration and sperm parameters (sperm concentration, progressive speed, anormal forms). Here, we detected for the first time GLY in the human seminal plasma in significant proportions and we showed that its concentration was four times higher than those observed in blood plasma. At the opposite, AMPA was undetectable. We also observed a strong positive correlation between plasma blood GLY concentrations and plasma seminal GLY and 8-OHdG concentrations, the latter reflecting DNA impact. In addition, TOS, Oxidative Stress Index (OSI) (TOS/TAS), MDA blood and seminal plasma concentrations were significantly higher in men with glyphosate in blood and seminal plasma, respectively. Taken together, our results suggest a negative impact of GLY on the human reproductive health and possibly on his progeny. A precaution principle should be applied at the time of the actual discussion of GLY and GBHs formulants uses in Europe by the authorities.
摘要：
环境暴露于内分泌干扰物，比如杀虫剂，可能导致人类生育能力下降。草甘膦(GLY)是草甘膦基除草剂(GBHs)的主要成分,这是世界上最常用的除草剂。各种动物模型研究证明了其生殖毒性。在欧洲,GLY农业授权已延长至2034年。同时，GLY对人类的毒性仍在争论中。本研究的目的是首先分析GLY及其主要代谢产物的浓度,通过LC/MS-MS在法国不育男性人群（n=128）的精液和血浆中进行氨基-甲基-膦酸（AMPA）。其次，我们使用商业比色试剂盒和一些氧化应激生物标志物，包括丙二醛（MDA）和8-羟基-2'-脱氧鸟苷（8-OHdG），通过ELISA测定确定总抗氧化状态（TAS）和总氧化状态（TOS）。我们接下来分析了GLY和氧化应激生物标志物浓度和精子参数(精子浓度，渐进速度，正常形式）。这里,我们首次在人类精浆中检测到显著比例的GLY，我们表明其浓度是血浆中观察到的浓度的四倍。在对面,AMPA检测不到。我们还观察到血浆血液GLY浓度与血浆精浆GLY和8-OHdG浓度之间存在很强的正相关性，后者反映了DNA的影响。此外,TOS,氧化应激指数（OSI）（TOS/TAS），丙二醛血和精浆浓度显著高于男性的草甘膦血和精浆，分别。一起来看,我们的结果表明GLY对人类生殖健康以及可能对其后代产生负面影响。在当局实际讨论GLY和GBHs配方在欧洲的使用时，应采用预防原则。
