Effects of Two Contraceptive Progestins on Reproductive Parameters in a Marine Fish
Citation:
Mills, L., S. Jayaraman, G. Zaroogian, Doranne Horowitz Borsay, T. Johnston, AND S. Laws. Effects of Two Contraceptive Progestins on Reproductive Parameters in a Marine Fish. Pollution Responses in Marine Organism (PRIMO), Charleston, South Carolina, May 19 - 22, 2019.
Impact/Purpose:
Progestins are major components of contraceptives that end up in human waste and run off into water bodies from sewage treatment plants. We evaluated what effects two common progestins, norethindrone and levonorgestrel, had on reproduction in the marine fish cunner (Tautogolabrus adspersus). Only norethindrone exposure significantly decreased egg production in spawning cunner, but both compounds altered activity of the enzyme that converts androgens to estrogens (i.e., aromatase). Only norethindrone was changed into the potent estrogen ethynylestradiol in cunner, which may partially explain the different effects of the two progestins. Ethynylestradiol is a powerful endocrine disrupting chemical that has been proven to negatively impact reproduction in fish.
Description:
Norethindrone (NET) and levonorgestrel (LNG) are progestins commonly found in human contraceptives. Progestins enter aquatic environments through excretion to and discharge from sewage treatment facilities, potentially causing effects in non-target organisms such as fish. The goal of our study was to evaluate the effects that NET and LNG exposure might have on egg production, viability and fertility in the marine fish cunner (Tautogolabrus adspersus). These reproductive endpoints were assessed daily in spawning cunner treated with nominal concentrations of 0, 0.075 or 0.75 mg/kg NET or LNG by oral gavage on days 0, 4, 8, 12 and 16 of a 17-day experiment. The activity of aromatase, the enzyme complex that converts androgens to estrogens in brains and ovaries of fish, was also assessed. In addition, to determine metabolism and clearance of LNG and NET, a time course experiment was conducted where blood was sampled periodically over 96 hours in cunner treated by gavage with a single dose of each progestin. Plasma samples were analyzed for LNG, NET, and a reported metabolite of NET, ethynylestradiol (EE2). While LNG treatments had no significant effect on reproductive endpoints in exposed cunner, cumulative egg production was significantly reduced in both NET treatments relative to controls. Gonadosomatic index (GSI) was also unaffected in LNG-treated fish, but GSI was significantly reduced in males and females from the 0.75 mg/kg NET treatment. Brains from male cunner exposed to 0.75 mg/kg LNG exhibited significantly decreased aromatase activity compared to controls, while females receiving both LNG treatments showed significantly increased ovarian aromatase activity. In contrast, 0.75 mg/kg NET increased male brain aromatase activity compared to controls. Ovarian aromatase activity was significantly increased in the low NET treatment, but not in the high NET treatment. The different effects of the two progestins may be partially explained by differences in metabolism. In samples from the time-course study, plasma from NET-treated fish was found to contain both NET and EE2. The pattern of EE2 measured in plasma over time suggests enterohepatic recirculation is occurring in NET-exposed cunner. In fact, only EE2 was detectable in plasma of NET-treated fish from the 17-day reproductive experiment. Results indicate EE2 is eliminated more slowly than either NET or LNG and may pose the greater risk to successful reproduction.