College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'an City 271018, Shandong Province, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City 271018, Shandong Province, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City 271018, Shandong Province, China.
New Drug Evaluation Center of Shandong Academy of Pharmaceutical Sciences, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Ji'nan City 250101, Shandong Province, China.
Sci Total Environ. 2022 Jan 20;805:150368. doi: 10.1016/j.scitotenv.2021.150368. Epub 2021 Sep 16.
Glyphosate (GLY), a ubiquitous environmental pollutant, can result in gut microbiota dysbiosis intimately involving various diseases. The latest research has shown an association between gut microbiota alteration and defective spermatogenesis. Here, we aimed to investigate whether GLY-induced gut microbiota dysbiosis contributed to male reproductive toxicity. Data showed that GLY-exposed rats exhibited male reproductive dysfunction, evidenced by impaired testis architectural structure, reduced sperm motility, together with increased sperm malformation ratio. 16S rDNA sequencing analysis indicated that GLY exposure altered the composition of gut commensal microbiota, of which the relative abundance of Bacteroidetes and Firmicutes phyla was significantly changed. Unexpectedly, the increased abundance of Prevotella_1 and Bacteroides genera was negatively correlated with sperm quality. Mechanistically, the pathological changes in GLY-exposed testis were accompanied by the increased interleukin (IL)-17A production, probably due to gut microbes-derived Th17 cell migration. Furthermore, activation of IL-17A signaling triggered testicular oxidative damage. Taken together, these findings uncover an underlying mechanistic scenario that gut microbiota dysbiosis-driven local IL-17A production is one reason responsible for male reproductive toxicity induced by GLY, which provides new insights into the male reproductive toxicity of GLY in mammals.
草甘膦（GLY）是一种普遍存在的环境污染物，可导致肠道微生物失调，与各种疾病密切相关。最新研究表明，肠道微生物失调与精子发生缺陷之间存在关联。在这里，我们旨在研究 GLY 诱导的肠道微生物失调是否导致男性生殖毒性。研究数据表明，暴露于 GLY 的大鼠表现出男性生殖功能障碍，其睾丸结构受损，精子运动能力降低，精子畸形率增加。16S rDNA 测序分析表明，GLY 暴露改变了肠道共生微生物的组成，其中厚壁菌门和拟杆菌门的相对丰度显著变化。出乎意料的是，Prevotella_1 和 Bacteroides 属的丰度增加与精子质量呈负相关。从机制上讲，暴露于 GLY 的睾丸的病理变化伴随着白细胞介素（IL）-17A 的产生增加，这可能是由于肠道微生物衍生的 Th17 细胞迁移所致。此外，IL-17A 信号的激活引发了睾丸的氧化损伤。总之，这些发现揭示了一种潜在的机制，即肠道微生物失调驱动局部产生的白细胞介素（IL）-17A 是 GLY 诱导男性生殖毒性的一个原因，这为哺乳动物中 GLY 的男性生殖毒性提供了新的见解。
