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Effects of metformin and its metabolite guanylurea on fathead minnow (Pimephales promelas) reproduction
Citation:
Blackwell, B., G. Ankley, J. Cavallin, A. Cole, A. Kittleson, M. Kahl, K. Jensen, C. Tilton, AND Dan Villeneuve. Effects of metformin and its metabolite guanylurea on fathead minnow (Pimephales promelas) reproduction. SETAC North America, Fort Worth, TX, November 15 - 19, 2020. https://doi.org/10.23645/epacomptox.13120208
Impact/Purpose:
Metformin (MET) is a commonly prescribed medication that is increasingly detected in the environment. Along with its primary metabolite, guanylurea (GU), there is growing concern for potential ecological effects of these compounds by disruption of reproduction in aquatic vertebrates. A standard Fish Short-Term Reproduction Assay (FSTRA) was conducted to assess potential reproductive effects of these two compounds on fathead minnows (Pimephales promelas). Spawning pairs of fathead minnows (n = 12) were exposed for 23 d to one of three nominal concentrations of each compound (0.41. 4.1, 41 µg/L MET; 1.0, 10, 100 µg/L GU) or control Lake Superior water. Fecundity of the fish was not impacted in any of the treatment groups. Our results suggest environmentally relevant concentrations of these compounds do not impact reproduction of adult fathead minnows.
Description:
Metformin (MET) is a drug commonly used for the treatment of type-2 diabetes. It is currently estimated to be among the top five most commonly prescribed drugs in the US. MET is not metabolized in humans; however, once excreted, the majority of MET is biotransformed to guanylurea (GU) during wastewater treatment. Given the widespread use of MET, both MET and GU are commonly detected in surface waters at low µg/L concentrations leading to concerns about their potential adverse ecological effects. Previous studies have documented an increase in intersex, reduction in fecundity, and alterations in development of teleost fish following exposure to MET or GU, further increasing concern for the two chemicals. To better characterize their potential ecological effects, we investigated impacts on reproduction in the fathead minnow (Pimephales promelas) using a fish short-term reproduction assay (FSTRA). Spawning pairs of fathead minnows (n = 12) were exposed for 23 d to one of three nominal concentrations of each compound (0.41. 4.1, 41 µg/L MET; 1.0, 10, 100 µg/L GU) or control Lake Superior water. Measured concentrations of MET and GU were within 25 and 10% of nominal, respectively. Fecundity of the fish was not impacted in any of the treatment groups. Several gene targets related to reproduction were measured in liver (esr1, vtg) or gonad (AR, cyp19a1, 3βhsd, 17βhsd) of males, but none of them were affected by either chemical. Overall, while MET and GU may be commonly detected in the environment, neither appear to impact reproduction of adult fathead minnows at environmentally relevant concentrations.
URLs/Downloads:
DOI: Effects of metformin and its metabolite guanylurea on fathead minnow (Pimephales promelas) reproduction