Glyphosate‐based herbicides (GBHs) are a group of widely used broad‐spectrum agricultural pesticides. Due to the recalcitrance of GBH, it has been found in food and environment as a contaminant, posing a threat to public health. The health risks associated with GBH have been indicated by reporting acute toxicity data (an acute exposure of GBH at a 0.5% dose), which primarily discuss toxicity in relation to accidental high‐rate exposure. Currently, there is little information regarding the toxicity of GBH at environmentally relevant levels. In this study, we used mature mouse oocytes to study the toxic effects of low‐dose GBH exposure in vitro (0.00001%–0.00025%) and in vivo (0.0005%, orally administered through daily drinking water) during meiotic maturation. GBH exposure led to meiotic maturation failure with spindle defects and chromosome misalignment. In addition, GBH treatment severely reduced sperm‐binding ability and disrupted early embryo cleavage. Moreover, GBH exposure significantly increased the reactive oxygen species (ROS) levels and apoptotic rates. Evidence indicates that such effects in GBH‐exposed oocytes are likely due to overexpression of the G‐protein estrogen receptor (GPER/GPR30). Remarkably, we found that melatonin administration elicited significant protection against GBH‐induced oocyte deterioration via preserving the expression of GPR30, along with activation of its downstream signaling event (pERK/ERK). Taken together, these results revealed that low‐dose glyphosate has a certain adverse effect on oocyte maturation and early embryo cleavage, and highlight the protective roles of melatonin.

中文翻译：

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褪黑素通过 GPER 信号通路挽救小鼠卵母细胞成熟过程中低剂量草甘膦除草剂的生殖毒性


草甘膦除草剂（GBH）是一组广泛使用的广谱农用农药。由于GBH的顽固性，已在食品和环境中作为污染物被发现，对公众健康构成威胁。与GBH相关的健康风险已通过报告急性毒性数据（0.5%剂量的GBH急性暴露）来表明，该数据主要讨论与意外高率暴露相关的毒性。目前，关于 GBH 在环境相关水平上的毒性的信息很少。在本研究中，我们使用成熟的小鼠卵母细胞来研究减数分裂成熟过程中低剂量 GBH 暴露的体外（0.00001%–0.00025%）和体内（0.0005%，通过每日饮用水口服）的毒性作用。 GBH 暴露导致减数分裂成熟失败，伴有纺锤体缺陷和染色体错位。此外，GBH 治疗严重降低了精子结合能力并破坏了早期胚胎分裂。此外，GBH 暴露显着增加了活性氧 (ROS) 水平和细胞凋亡率。有证据表明，GBH 暴露的卵母细胞中的这种效应可能是由于 G 蛋白雌激素受体 (GPER/GPR30) 的过度表达所致。值得注意的是，我们发现褪黑素给药通过保留 GPR30 的表达以及激活其下游信号事件 (pERK/ERK)，可显着防止 GBH 诱导的卵母细胞退化。综上所述，这些结果揭示了低剂量草甘膦对卵母细胞成熟和早期胚胎卵裂有一定的不利影响，并凸显了褪黑激素的保护作用。