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Series GSE198081 Query DataSets for GSE198081
Status Public on Mar 03, 2023
Title Effects of metformin and its metabolite guanylurea on fathead minnow (Pimephales promelas) reproduction
Organism Pimephales promelas
Experiment type Expression profiling by high throughput sequencing
Summary Metformin, along with its biotransformation product guanylurea, are commonly observed in municipal wastewaters and subsequent surface waters. Previous studies in fish have identified metformin as a potential endocrine active compound but there are inconsistencies in the literature with regard to effects. To further investigate the potential reproductive toxicity of metformin and guanylurea to fish, a series of experiments were performed with reproductively mature fathead minnows (Pimephales promelas). First, explants of mature fathead minnow ovary tissue were exposed to 0.001-100 µM metformin or guanylurea to investigate whether they can directly perturb steroidogenesis. Second, spawning pairs of fathead minnows were exposed to metformin (0.41, 4.1, 41 µg/L) or guanylurea (1.0, 10, 100 µg/L) for 23 d to assess impacts on reproduction. Lastly, male fathead minnows were exposed to 41 µg/L metformin, 100 µg/L guanylurea, or a mixture of both compounds, with samples collected over a 96 h time course to investigate potential impacts to the hepatic transcriptome or metabolome. Neither metformin or guanylurea effected estradiol or testosterone by ovary tissue exposed in vitro. In the 23 d exposure, neither compound significantly impacted transcription of endocrine-related genes in male liver or gonad, circulating steroid concentrations in male or female fish, or fecundity of spawning pairs. In the 96 h time course, 100 µg guanylurea/L elicited more differential gene expression than 41 µg metformin/L , and showed the greatest impacts after 96 h. A number of DEGs up-regulated after 24 h were subsequently down-regulated after 96 h, demonstrating time-dependent impacts of guanylurea on the liver. Overall, metformin and guanylurea did not elicit effects consistent with reproductive toxicity in adult fathead minnows at environmentally relevant concentrations. Where effects were identified using ‘omics approaches, guanylurea induced greater impacts than metformin.
Overall design Male fathead minnows were exposed to 41 µg/L metformin, 100 µg/L guanylurea, or a mixture of both compounds, with samples collected over a 96h time course to investigate transcriptome responses from exposure
Contributor(s) Huang W, See MJ, Biales AD, Blackwell BR, Ankley GT, Cavallin JE, Cole AR, Collette TW, Ekman DR, Hofe RN, Jensen KM, Kahla MD, Kittelsonc AR, Romanod S, Tengd Q, Tilton CB, Villeneuve DL
Citation(s) 35920346
Submission date Mar 07, 2022
Last update date Jun 02, 2023
Contact name Weichun Huang
Organization name US EPA
Department ORD
Street address 109 TW Alexander Dr
City Durham
State/province NC
ZIP/Postal code 27711
Country USA
Platforms (1)
GPL25572 Illumina HiSeq 4000 (Pimephales promelas)
Samples (191)
GSM5938351 Control_6_1
GSM5938352 Control_6_2
GSM5938353 Control_6_3
BioProject PRJNA813573

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Supplementary file Size Download File type/resource
GSE198081_metGU_RSEM_read_count_genes.txt.gz 5.2 Mb (ftp)(http) TXT
GSE198081_metGU_RSEM_read_count_transcripts.txt.gz 7.1 Mb (ftp)(http) TXT
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