State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Chemosphere. 2022 Jan;287(Pt 4):132395. doi: 10.1016/j.chemosphere.2021.132395. Epub 2021 Sep 28.
Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its neural and reproductive toxicity. To uncover potential effects of GLA on male reproductive health in mammals, adult male C57BL/6J mice were administered 0.2 mg/kg·d GLA for 5 weeks. After examination on fertility, testis histology and semen quality in the GLA group, we performed deep sequencing to identify repressive epigenetic marks including DNA methylation and histone modifications (H3K27me3 and H3K9me3), together with mRNA transcript levels in sperm. Then, we integrated multi-omics sequencing data to comprehensively explore GLA-induced epigenetic and transcriptomic alterations. We found no significant difference either on fertility, testis histology or semen quality-related indicators. As for epigenome, the protein level of H3K27me3 was significantly increased in GLA sperm. Next generation sequencing showed alterations of these epigenetic marks and extensive transcription inhibition in sperm. These differential repressive marks were mainly distributed at intergenic regions and introns. According to results by Gene Ontology enrichment analysis, both differentially methylated and expressed genes were mainly enriched in pathways related to synapse organization. Subtle differences in genomic imprinting were also observed between the two groups. These results suggested that GLA predominantly impaired sperm epigenome and transcriptome in mice, with little effect on fertility, testis histology or semen quality. Further studies on human sperm using similar strategies need to be conducted for a better understanding of the male reproductive toxicity of GLA.
草铵膦（GLA）是一种广泛使用的除草剂，其神经毒性和生殖毒性受到越来越多的关注。为了揭示 GLA 对哺乳动物雄性生殖健康的潜在影响，将成年雄性 C57BL/6J 小鼠用 0.2mg/kg·d GLA 处理 5 周。在 GLA 组进行生育力、睾丸组织学和精液质量检查后，我们进行了深度测序，以鉴定包括 DNA 甲基化和组蛋白修饰（H3K27me3 和 H3K9me3）在内的抑制性表观遗传标记，以及精子中的 mRNA 转录水平。然后，我们整合了多组学测序数据，全面探讨了 GLA 诱导的表观遗传和转录组改变。我们没有发现生育力、睾丸组织学或精液质量相关指标有显著差异。至于表观基因组，GLA 精子中的 H3K27me3 蛋白水平显著增加。下一代测序显示这些表观遗传标记和精子中广泛的转录抑制发生改变。这些差异抑制标记主要分布在基因间区和内含子。根据基因本体论富集分析的结果，差异甲基化和表达基因主要富集在与突触组织相关的途径中。两组之间也观察到基因组印迹的细微差异。这些结果表明，GLA 主要损害了小鼠精子的表观基因组和转录组，对生育力、睾丸组织学或精液质量几乎没有影响。需要使用类似的策略对人类精子进行进一步研究，以更好地了解 GLA 的雄性生殖毒性。
