title: Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish.
abstract: Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms.
authors.affiliation: School of Freshwater Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Niemuth
authors.forename: Renee
authors.initials: R
authors.lastname: Jordan
authors.forename: Jordan
authors.initials: J
authors.lastname: Crago
authors.forename: Chad
authors.initials: C
authors.lastname: Blanksma
authors.forename: Rodney
authors.initials: R
authors.lastname: Johnson
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Klaper
mesh_terms: D000818:Animals; D003530:Cyprinidae / Q000097:blood / Q000235:genetics / Q000502:physiology*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008658:Inactivation, Metabolic / Q000187:drug effects / Q000235:genetics; D008297:Male; D008687:Metformin / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D014819:Vitellogenins / Q000097:blood / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014922:Wisconsin
chemical_list: D052244:Endocrine Disruptors; D012333:RNA, Messenger; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D013739:Testosterone; D008687:Metformin
keywords: Contaminants of emerging concern; Endocrine disruptors; Metformin; Pharmaceuticals; Reproductive toxicity