The unsustainable use of manmade chemicals poses significant threats to biodiversity and human health. Emerging evidence highlights the potential of certain chemicals to cause transgenerational impacts on metabolic health. Here, we investigate male transmitted epigenetic transgenerational effects of the anti-androgenic herbicide linuron in the pancreas of frogs, and their association with metabolic phenotypes. Reduced representation bisulfite sequencing (RRBS) was used to assess genome-wide DNA methylation patterns in the pancreas of adult male F2 generation ancestrally exposed to environmentally relevant linuron levels (44 ± 4.7 μg/L). We identified 1117 differentially methylated regions (DMRs) distributed across the genome, revealing potential regulatory mechanisms underlying metabolic disturbances. DMRs were identified in genes crucial for pancreatic function, including calcium signalling ( and ), genes associated with type 2 diabetes ( and ) and a biomarker for pancreatic ductal adenocarcinoma (). Correlation analysis revealed associations between DNA methylation levels in these genes and metabolic phenotypes, indicating epigenetic regulation of glucose metabolism. Moreover, differential methylation in genes related to histone modifications suggests alterations in the epigenetic machinery. These findings underscore the long-term consequences of environmental contamination on pancreatic function and raise concerns about the health risks associated with transgenerational effects of pesticides.

中文翻译：

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热带非洲爪蟾胰腺中农药诱导的全基因组 DNA 甲基化模式的跨代改变与代谢表型相关


人造化学品的不可持续使用对生物多样性和人类健康构成重大威胁。新的证据强调了某些化学物质对代谢健康造成跨代影响的潜力。在这里，我们研究了抗雄激素除草剂利谷隆在青蛙胰腺中的雄性遗传表观遗传跨代效应，及其与代谢表型的关联。使用简化代表性亚硫酸氢盐测序 (RRBS) 来评估祖先暴露于环境相关利谷隆水平 (44 ± 4.7 μg/L) 的成年雄性 F2 代胰腺中的全基因组 DNA 甲基化模式。我们鉴定了分布在基因组中的 1117 个差异甲基化区域 (DMR)，揭示了代谢紊乱的潜在调控机制。 DMR 在对胰腺功能至关重要的基因中被发现，包括钙信号传导 ( 和 )、与 2 型糖尿病相关的基因 ( 和 ) 以及胰腺导管腺癌的生物标志物 ( )。相关分析揭示了这些基因中 DNA 甲基化水平与代谢表型之间的关联，表明葡萄糖代谢的表观遗传调控。此外，与组蛋白修饰相关的基因的差异甲基化表明表观遗传机制的改变。这些发现强调了环境污染对胰腺功能的长期影响，并引起了人们对农药跨代效应相关健康风险的担忧。