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首页> 外文期刊>Environmental toxicology and chemistry / >Effects of Metformin and its Metabolite Guanylurea on Fathead Minnow (Pimephales promelas) Reproduction
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Effects of Metformin and its Metabolite Guanylurea on Fathead Minnow (Pimephales promelas) Reproduction

机译：Effects of Metformin and its Metabolite Guanylurea on Fathead Minnow (Pimephales promelas) Reproduction

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Metformin, along with its biotransformation product guanylurea, is commonly observed in municipal wastewaters andsubsequent surface waters. Previous studies in fish have identified metformin as a potential endocrine‐active compound, butthere are inconsistencies with regard to its effects. To further investigate the potential reproductive toxicity of metformin andguanylurea to fish, a series of experiments was performed with adult fathead minnows (Pimephales promelas). First, explants offathead minnow ovary tissue were exposed to 0.001–100 μM metformin or guanylurea to investigate whether the compoundscould directly perturb steroidogenesis. Second, spawning pairs of fathead minnows were exposed to metformin (0.41, 4.1, and41 μg/L) or guanylurea (1.0, 10, and 100 μg/L) for 23 days to assess impacts on reproduction. Lastly, male fathead minnows wereexposed to 41 μg/L metformin, 100μg/L guanylurea, or a mixture of both compounds, with samples collected over a 96‐h timecourse to investigate potential impacts to the hepatic transcriptome or metabolome. Neither metformin nor guanylureaaffected steroid production by ovary tissue exposed ex vivo. In the 23 days of exposure, neither compound significantlyimpacted transcription of endocrine‐related genes in male liver or gonad, circulating steroid concentrations in either sex, orfecundity of spawning pairs. In the 96‐h time course, 100 μg guanylurea/L elicited more differentially expressed genes than41 μg metformin/L and showed the greatest impacts at 96 h. Hepatic transcriptome and metabolome changes were chemicalandtime‐dependent, with the largest impact on the metabolome observed at 23 days of exposure to 100 μg guanylurea/L.Overall, metformin and guanylurea did not elicit effects consistent with reproductive toxicity in adult fathead minnows atenvironmentally relevant concentrations.

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