Metformin is one of the most prevalent pharmaceuticals in both surface and waste waters, yet little is known about the bioavailability and/or effects of developmental exposure on early life stage (ELS) fish. Here, we demonstrate that embryo-larval stages of medaka are capable of taking up metformin from the aquatic environment, provided exposure occurs prior to chorion hardening (∼6-hpf). Once transferred to clean water, ELS medaka are able to completely depurate metformin in <24-hours. Furthermore, ELS medaka exposed to a range of relevant concentrations of waterborne metformin (from 6 hpf through 28-days post hatch) had significantly reduced growth metrics, altered metabolomes, and changes in the expression of genes associated with cell growth. The range of concentrations investigated were 1.0, 3.2, 10, 32, and 100 μg·L⁻¹. To examine effects of chronic, low level metformin exposure across the full medaka life-cycle, we exposed newly fertilized embryos to 3.2 μg L⁻¹ waterborne metformin for 165-days. The weight and length of adult fish were examined, as were effects on the production of some steroid hormones, specifically a significant increase (control females: 0.161 ± 0.023 pg/mg; metformin treated females: 3.42 ± 0.543) in the production of 11-ketotestosterone was observed in adult female medaka. Collectively, these results suggest that current environmental exposure scenarios may be sufficient to cause effects on developing fish.

二甲双胍是地表水和废水中最流行的药物之一，但对于发育期暴露（ELS）鱼的生物利用度和/或发育暴露的影响知之甚少。在这里，我们证明，只要暴露在绒毛膜硬化之前（〜6-hpf）之前发生，高的幼虫阶段就能从水生环境中吸收二甲双胍。一旦转移到纯净水中，ELS medaka就能在不到24小时的时间内完全净化二甲双胍。此外，ELS medaka暴露于一系列相关浓度的水性二甲双胍（从孵化后6 hpf至28天），具有显着降低的生长指标，改变了代谢组以及与细胞生长相关的基因表达变化。研究的浓度范围为1.0、3.2、10、32和100μg·L^-1。为了检验整个medaka生命周期中慢性低水平二甲双胍暴露的影响，我们将新受精的胚胎暴露于3.2μgL ^-1水性二甲双胍中165天。检查了成年鱼的体重和长度，以及对某些类固醇激素产生的影响，特别是在11-生产中显着增加（雌性对照：0.161±0.023 pg / mg；二甲双胍处理的雌性：3.42±0.543）。在成年雌性med中观察到了酮睾酮。总的来说，这些结果表明，当前的环境暴露情景可能足以对发育中的鱼类造成影响。