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Mode of action evaluation for reduced reproduction in Daphnia pulex exposed to the insensitive munition, 1-methyl-3-nitro-1-nitroguanidine (MeNQ)
Ecotoxicology ( IF 2.4 ) Pub Date : 2021-06-26 , DOI: 10.1007/s10646-021-02447-w
Kurt A. Gust , Guilherme R. Lotufo , Natalie D. Barker , Qing Ji , Lauren K. May

The US Department of Defense (DOD) is developing insensitive munitions (IMs) that are resistant to unintended detonation to protect warfighters. To enable material life-cycle analysis for the IM, 1-methyl-3-nitro-1-nitroguanidine (MeNQ), ecotoxicological impacts assessment was required. A previous investigation of MeNQ exposures in Daphnia pulex revealed concentration-responsive decreases in reproduction relative to controls (0 mg/L) across a 174, 346, 709, 1385, and 2286 mg/L exposure range. The present study used those exposures to conduct global transcriptomic expression analyses to establish hypothetical mode(s) of action underlying inhibited reproduction. The number of significantly affected transcripts and the magnitude of fold-change differences relative to controls tended to increase with increasing MeNQ concentration where hierarchical clustering analysis identified separation among the “low” (174 and 346 mg/L) and “high” (709, 1385, and 2286 mg/L) exposures. Vitellogenin is critical to Daphnia reproductive processes and MeNQ exposures significantly decreased transcriptional expression for vitellogenin-1 precursor at the lowest exposure level (174 mg/L) with benchmark dose (BMD) levels closely tracking concentrations that caused inhibited reproduction. Additionally, juvenile hormone-inducible protein, chorion peroxidase, and high choriolytic enzyme transcriptional expression were impacted by MeNQ exposure having potential implications for egg production / maturation and overall fecundity. In concert with these effects on specific genes involved in Daphnia reproductive physiology, MeNQ exposures caused significant enrichment of several canonical-pathways responsible for metabolism of cellular energy substrates where BMD levels for transcriptional expression were observed at ≤100 mg/L. These observations imply possible effects on whole-organism energy budgets that may also incur indirect costs on reproduction.



中文翻译:

对暴露于不敏感弹药 1-甲基-3-硝基-1-硝基胍 (MeNQ) 的 Daphnia pulex 减少繁殖的作用方式评估

美国国防部 (DOD) 正在开发能够抵抗意外爆炸的钝感弹药 (IM),以保护作战人员。为了能够对 IM、1-甲基-3-硝基-1-硝基胍 (MeNQ) 进行材料生命周期分析,需要进行生态毒理学影响评估。先前对水中 MeNQ 暴露的调查揭示了在 174、346、709、1385 和 2286 毫克/升暴露范围内,繁殖相对于对照 (0 毫克/升) 的浓度响应性下降。本研究使用这些暴露进行全局转录组表达分析,以建立抑制繁殖的假设作用模式。显着影响的转录物数量和相对于对照的倍数变化差异的幅度往往随着 MeNQ 浓度的增加而增加,其中层次聚类分析确定了“低”(174 和 346 毫克/升)和“高”(709, 1385 和 2286 毫克/升)暴露。卵黄蛋白原对水蚤至关重要生殖过程和 MeNQ 暴露显着降低了最低暴露水平 (174 mg/L) 下卵黄蛋白原 1 前体的转录表达,基准剂量 (BMD) 水平密切跟踪导致抑制繁殖的浓度。此外,保幼激素诱导蛋白、绒毛膜过氧化物酶和高绒毛膜溶解酶转录表达受到 MeNQ 暴露的影响,对产蛋/成熟和整体繁殖力有潜在影响。与对参与水蚤的特定基因的这些影响一致在生殖生理学方面,MeNQ 暴露导致几种负责细胞能量底物代谢的经典途径显着富集,其中观察到转录表达的 BMD 水平≤100 毫克/升。这些观察结果暗示了对整个生物体能量预算的可能影响,这些影响也可能导致繁殖的间接成本。

更新日期:2021-07-22
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