Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish

Environmental Toxicology and Chemistry

Volumn 34, Issue 2, 2015, Pages 291-296

  Niemuth, Nicholas J ^a   Jordan, Renee ^a   Crago, Jordan ^a   Blanksma, Chad ^b   Johnson, Rodney ^b   Klaper, Rebecca D ^a  

^a UNIVERSITY OF WISCONSIN MILWAUKEE   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Contaminants of emerging concern; Endocrine disruptors; Metformin; Pharmaceuticals; Reproductive toxicity

Indexed keywords

AQUATIC ORGANISMS; DRUG PRODUCTS; EFFLUENT TREATMENT; ENDOCRINE DISRUPTERS; FISH; METABOLISM; NUCLEIC ACIDS; PHYSIOLOGY; RNA; SURFACE WATERS; TOXICITY; WASTE TREATMENT; WASTEWATER TREATMENT; WATER POLLUTION;

AQUATIC ENVIRONMENTS; CONTAMINANTS OF EMERGING CONCERNS; ENDOCRINE DISRUPTION; ENDOCRINE DISRUPTOR; METFORMINS; PHARMACEUTICALS AND PERSONAL CARE PRODUCTS; REPRODUCTIVE TOXICITIES; WASTEWATER TREATMENT PLANTS;

EFFLUENTS;

METFORMIN; ENDOCRINE DISRUPTOR; MESSENGER RNA; TESTOSTERONE; VITELLOGENIN; WATER POLLUTANT;

ADULT; AQUATIC ENVIRONMENT; AQUATIC ORGANISM; CONCENTRATION (COMPOSITION); CYPRINID; DRUG; EFFLUENT; ENDOCRINE DISRUPTOR; EXCRETION; FISH; MALE; ORGANIC ACID; POLLUTANT SOURCE; POLLUTION EXPOSURE; REPRODUCTION; TOXICITY;

ADULT; ANIMAL EXPERIMENT; AQUATIC ENVIRONMENT; AQUATIC SPECIES; ARTICLE; CONTROLLED STUDY; EFFLUENT; EGG PRODUCTION; ENDOCRINE FUNCTION; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL PROTECTION; FISH; HORMONE BLOOD LEVEL; MALE; METABOLISM; NONHUMAN; PIMEPHALES PROMELAS; PRIORITY JOURNAL; REPRODUCTION; STEROIDOGENESIS; WASTE WATER TREATMENT PLANT; ANIMAL; BLOOD; CYPRINIDAE; DRUG EFFECTS; DRUG INACTIVATION; FEMALE; GENE EXPRESSION REGULATION; GENETICS; PHYSIOLOGY; TOXICITY; UNITED STATES; WATER POLLUTANT;

UNITED STATES; WISCONSIN;

PIMEPHALES PROMELAS;

ANIMALS; CYPRINIDAE; ENDOCRINE DISRUPTORS; ENVIRONMENTAL EXPOSURE; FEMALE; GENE EXPRESSION REGULATION; INACTIVATION, METABOLIC; MALE; METFORMIN; REPRODUCTION; RNA, MESSENGER; TESTOSTERONE; VITELLOGENINS; WATER POLLUTANTS, CHEMICAL; WISCONSIN;

EID: 84922601260     PISSN: 07307268     EISSN: 15528618     Source Type: Journal    
DOI: 10.1002/etc.2793     Document Type: Article

References (39)

1. Blair BD, Crago JP, Hedman CJ, Klaper RD. 2013. Pharmaceuticals and personal care products found in the Great Lakes above concentrations of environmental concern. Chemosphere 93:2116-2123.
2. Boyd GR, Reemtsma H, Grimm DA, Mitra S. 2003. Pharmaceuticals and personal care products (PPCPs) in surface and treated waters of Louisiana, USA and Ontario, Canada. Sci Total Environ 311:135-149.
3. Oosterhuis M, Sacher F, Ter Laak TL. 2013. Prediction of concentration levels of metformin and other high consumption pharmaceuticals in wastewater and regional surface water based on sales data. Sci Total Environ 442:380-388.
4. Ternes TA. 1998. Occurrence of drugs in German sewage treatment plants and rivers. 1. Dedicated to Professor Dr. Klaus Haberer on the occasion of his 70th birthday. Water Res 32:3245-3260.
5. Fatta-Kassinos D, Meric S, Nikolaou A. 2011. Pharmaceutical residues in environmental waters and wastewater: Current state of knowledge and future research. Anal Bioanal Chem 399:251-275.
6. Heberer T. 2002. Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: A review of recent research data. Toxicol Lett 131:5-17.
7. Blair BD, Crago JP, Hedman CJ, Treguer RJF, Magruder C, Royer LS, Klaper RD. 2013. Evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater. Sci Total Environ 444:515-521.
8. Al Aukidy, Verlicchi M, Jelic P, Petrovic A, Barcelò M. 2012. Monitoring release of pharmaceutical compounds: Occurrence and environmental risk assessment of two WWTP effluents and their receiving bodies in the Po Valley, Italy. Sci Total Environ 438:15-25.
9. Weinberger J, Klaper R. 2013. Environmental concentrations of the selective serotonin reuptake inhibitor fluoxetine impact specific behaviors involved in reproduction, feeding and predator avoidance in the fish Pimephales promelas (fathead minnow). Aquat Toxicol 151:77-83.
10. Scheurer M, Michel A, Brauch H-J, Ruck W, Sacher F. 2012. Occurrence and fate of the antidiabetic drug metformin and its metabolite guanylurea in the environment and during drinking water treatment. Water Res 46:4790-4802.
11. Ghoshdastidar AJ, Fox S, Tong AZ. 2014. The presence of the top prescribed pharmaceuticals in treated sewage effluents and receiving waters in Southwest Nova Scotia, Canada. Environ Sci Pollut Res Int DOI:10.1007/s11356-014-3400-z
12. Ben Sahra, Le Marchand-Brustel Y, Tanti J-F, Bost F. 2010. Metformin in cancer therapy: A new perspective for an old antidiabetic drug? Mol Cancer Ther 9:1092-1099.
13. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. 2012. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 5:CD003053.
14. Viollet B, Guigas B, Sanz Garcia, Leclerc N, Foretz J, Andreelli M. 2012. Cellular and molecular mechanisms of metformin: An overview. Clin Sci 122:253-270.
15. Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS. 2005. Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod 20:1820-1826.
16. Blazer VS, Iwanowicz LR, Henderson H, Mazik PM, Jenkins JA, Alvarez DA, Young JA. 2012. Reproductive endocrine disruption in smallmouth bass (Micropterus dolomieu) in the Potomac River basin: Spatial and temporal comparisons of biological effects. Environ Monit Assess 184:4309-4334.
17. Jobling S, Burn RW, Thorpe K, Williams R, Tyler C. 2009. Statistical modeling suggests that antiandrogens in effluents from wastewater treatment works contribute to widespread sexual disruption in fish living in English rivers. Environ Health Perspect 117:797-802.
18. Panserat S, Skiba-Cassy S, Seiliez I, Lansard M, Plagnes-Juan E, Vachot C, Aguirre P, Larroquet L, Chavernac G, Medale F, Corraze G, Kaushik S, Moon TW. 2009. Metformin improves postprandial glucose homeostasis in rainbow trout fed dietary carbohydrates: A link with the induction of hepatic lipogenic capacities? Am J Physiol Regul Integr Comp Physiol 297:R707-R715.
19. Polakof S, Moon TW, Aguirre P, Skiba-Cassy S, Panserat S. 2011. Glucose homeostasis in rainbow trout fed a high-carbohydrate diet: Metformin and insulin interact in a tissue-dependent manner. Am J Physiol Regul Integr Comp Physiol 300:R166-R174.
20. Polakof S, Skiba-Cassy S, Panserat S. 2009. Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout. Am J Physiol Regul Integr Comp Physiol 297:R1769-R1776.
21. Polakof S, Panserat S, Craig PM, Martyres DJ, Plagnes-Juan E, Savari S, Aris-Brosou S, Moon TW. 2011. The metabolic consequences of hepatic AMP-kinase phosphorylation in rainbow trout. PLoS One 6: e 20228.
22. Elo B, Villano CM, Govorko D, White LA. 2007. Larval zebrafish as a model for glucose metabolism: Expression of phosphoenolpyruvate carboxykinase as a marker for exposure to anti-diabetic compounds. J Mol Endocrinol 38:433-440.
23. Lattier DL, Reddy TV, Gordon DA, Lazorchak JM, Smith ME, Williams DE, Wiechman B, Flick RW, Miracle AL, Toth GP. 2002. 17alpha-ethynylestradiol-induced vitellogenin gene transcription quantified in livers of adult males, larvae, and gills of fathead minnows (Pimephales promelas). Environ Toxicol Chem 21:2385-2393.
24. Ankley GT, Jensen KM, Kahl MD, Korte JJ, Makynen EA. 2001. Description and evaluation of a short-term reproduction test with the fathead minnow (Pimephales promelas). Environ Toxicol Chem 20:1276-1290.
25. Fulgencio JP, Kohl C, Girard J, Pégorier JP. 2001. Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes. Biochem Pharmacol 62:439-446.
26. Bhalla K, Hwang BJ, Dewi RE, Twaddel W, Goloubeva OG, Wong K-K, Saxena NK, Biswal S, Girnun GD. 2012. Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev Res (Phila) 5:544-552.
27. Crago J, Klaper R. 2012. A mixture of an environmentally realistic concentration of a phthalate and herbicide reduces testosterone in male fathead minnow (Pimephales promelas) through a novel mechanism of action. Aquat Toxicol 110-111 74-83.
28. Klaper R, Rees CB, Drevnick P, Weber D, Sandheinrich M, Carvan MJ. 2006. Gene expression changes related to endocrine function and decline in reproduction in fathead minnow (Pimephales promelas) after dietary methylmercury exposure. Environ Health Perspect 114:1337-1343.
29. Skolness SY, Durhan EJ, Jensen KM, Kahl MD, Makynen EA, Villeneuve DL, Ankley GT. 2012. Effects of gemfibrozil on lipid metabolism, steroidogenesis, and reproduction in the fathead minnow (Pimephales promelas). Environ Toxicol Chem 31:2615-2624.
30. Muncke J, Eggen RIL. 2006. Vitellogenin 1 mRNA as an early molecular biomarker for endocrine disruption in developing zebrafish (Danio rerio). Environ Toxicol Chem 25:2734-2741.
31. Schmid T, Gonzalez-Valero J, Rufli H, Dietrich DR. 2002. Determination of vitellogenin kinetics in male fathead minnows (Pimephales promelas). Toxicol Lett 131:65-74.
32. Länge R, Hutchinson TH, Croudace CP, Siegmund F, Schweinfurth H, Hampe P, Panter GH, Sumpter JP. 2001. Effects of the synthetic estrogen 17α-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas). Environ Toxicol Chem 20:1216-1227.
33. Levi L, Pekarski I, Gutman E, Fortina P, Hyslop T, Biran J, Levavi-Sivan B, Lubzens E. 2009. Revealing genes associated with vitellogenesis in the liver of the zebrafish (Danio rerio) by transcriptome profiling. BMC Genom 10:141.
34. Owen SF, Giltrow E, Huggett DB, Hutchinson TH, Saye J, Winter MJ, Sumpter JP. 2007. Comparative physiology, pharmacology and toxicology of beta-blockers: Mammals versus fish. Aquat Toxicol 82:145-162.
35. Proctor WR, Bourdet DL, Thakker DR. 2008. Mechanisms underlying saturable intestinal absorption of metformin. Drug Metab Dispos 36:1650-1658.
36. Evans DH. 1987. The fish gill: Site of action and model for toxic effects of environmental pollutants. Environ Health Perspect 71:47-58.
37. Crago J, Klaper RD. 2011. Influence of gender, feeding regimen, and exposure duration on gene expression associated with xenobiotic metabolism in fathead minnows (Pimephales promelas). Comp Biochem Physiol C Toxicol Pharmacol 154:208-212.
38. Bainy ACD, Kubota A, Goldstone JV, Lille-Langøy R, Karchner SI, Celander MC, Hahn ME, Goksøyr A, Stegeman JJ. 2013. Functional characterization of a full length pregnane X receptor, expression in vivo, and identification of PXR alleles, in zebrafish (Danio rerio). Aquat Toxicol 142-143:447-457.
39. Beitel SC, Doering JA, Patterson SE, Hecker M. 2014. Assessment of the sensitivity of three North American fish species to disruptors of steroidogenesis using in vitro tissue explants. Aquat Toxicol 152:273-283.