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Effects of Norethindrone and Metabolite Ethynylestradiol on Reproductive Parameters in a Marine Fish
Citation:
Mills, L., Saro Jayaraman, G. Zaroogian, D. Borsay, T. Johnston, AND S. Laws. Effects of Norethindrone and Metabolite Ethynylestradiol on Reproductive Parameters in a Marine Fish. Society of Toxicology (SOT) 55th Annual Meeting, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
This abstract will be submitted to the Society of Toxicology (SOT) for consideration as the basis of a poster presentation to be given at the March 2016 meeting. The abstract and poster will summarize research that has been completed investigating the effects of the human contraceptive norethindrone on a marine fish species.
Description:
Norethindrone (NOR) is a progestin used in human contraceptives and has been detected in low concentrations (ng/L) in aquatic environments. Laboratory experiments were conducted with the marine fish cunner (Tautogolabrus adspersus) to evaluate whether NOR could affect reproductive success. Egg production, viability and fertility were assessed daily in spawning cunner treated with nominal concentrations of 0, 0.075 or 0.75 mg/kg NOR by oral gavage on days 0, 4, 8, 12 and 16 of the experiment. Fish were sacrificed on day 17 and gonadosomatic index (GSI) was determined. Brains and ovaries from all fish were flash-frozen for later determination of microsomal aromatase activity. In both NOR treatments, egg production per gram female was significantly reduced relative to controls, while GSI was significantly reduced in males and females from the 0.75 mg/kg treatment. Female mortality in 0.75 mg/kg treatment was more than twice that in controls, suggesting an increase in male aggression. Relative to controls, NOR treatment did not affect aromatase activity in female brains, but significantly decreased aromatase activity in ovaries and male brains. During a separate time-course exposure, plasma of NOR-treated cunner was found to contain both NOR and ethynylestradiol (EE2). Thirty minutes after a single gavage with 7.5 mg/kg NOR, plasma concentrations of NOR averaged 370 ng/ml, while EE2 averaged 18.7 ng/ml. By 24 hours after gavage, the average plasma concentration of NOR dropped to 2.7 ng/ml, while EE2 was 9.7 ng/ml. The pattern of EE2 measured in fish plasma over time suggests enterohepatic recirculation of EE2 is occurring in NOR-exposed cunner. Results indicate the metabolite EE2 is eliminated more slowly than NOR and may pose the greater risk to reproductive success in this marine fish. This abstract does not reflect U.S. EPA policy.