Doering Jon A, Villeneuve Daniel L, Tilton Charlene B, Kittelson Ashley R, Blackwell Brett R, Kahl Michael D, Jensen Kathleen M, Poole Shane T, Cavallin Jenna E, Cole Alexander R, Dean Kendra N, LaLone Carlie A, Ankley Gerald T
National Research Council, 6201 Congdon Boulevard, Duluth, MN, 55804, United States.
Great Lakes Toxicology and Ecology Division, U.S. Environmental Protection Agency, 6201 Congdon Boulevard, Duluth, MN, 55804, United States.
Aquat Toxicol. 2021 Jan 5;232:105741. doi: 10.1016/j.aquatox.2020.105741.
Exposure to certain anthropogenic chemicals can inhibit the activity to cytochrome P450 aromatase (CYP19) in fishes leading to decreased plasma 17β-estradiol (E2), plasma vitellogenin (VTG), and egg production. Reproductive dysfunction resulting from exposure to aromatase inhibitors has been extensively investigated in several laboratory model species of fish. These model species have ovaries that undergo asynchronous oocyte development, but many fishes have ovaries with group-synchronous oocyte development. Fishes with group-synchronous oocyte development have dynamic reproductive cycles which typically occur annually and are often triggered by complex environmental cues. This has resulted in a lack of test data and uncertainty regarding sensitivities to and adverse effects of aromatase inhibition. The present study used the western mosquitofish (Gambusia affinis) as a laboratory model to investigate adverse effects of chemical aromatase inhibition on group-synchronous oocyte development. Adult female western mosquitofish were exposed to either 0, 2, or 30 μg/L of the model nonsteroidal aromatase inhibiting chemical, fadrozole, for a complete reproductive cycle. Fish were sampled at four time-points representing pre-vitellogenic resting, early vitellogenesis, late vitellogenesis/early ovarian recrudescence, and late ovarian recrudescence. Temporal changes in numerous reproductive parameters were measured, including gonadosomatic index (GSI), plasma sex steroids, and expression of selected genes in the brain, liver, and gonad that are important for reproduction. In contrast to fish from the control treatment, fish exposed to 2 and 30 μg/L of fadrozole had persistent elevated expression of cyp19 in the ovary, depressed expression of vtg in the liver, and a low GSI. These responses suggest that completion of a group-synchronous reproductive cycle was unsuccessful during the assay in fish from either fadrozole treatment. These adverse effects data show that exposure to aromatase inhibitors has the potential to cause reproductive dysfunction in a wide range of fishes with both asynchronous and group-synchronous reproductive strategies.
接触某些人为化学物质会抑制鱼类细胞色素P450芳香化酶（CYP19）的活性，导致血浆17β-雌二醇（E2）、血浆卵黄蛋白原（VTG）水平降低以及产卵量减少。在几种鱼类实验室模型物种中，对接触芳香化酶抑制剂导致的生殖功能障碍进行了广泛研究。这些模型物种的卵巢经历异步卵母细胞发育，但许多鱼类的卵巢具有群体同步卵母细胞发育。具有群体同步卵母细胞发育的鱼类具有动态生殖周期，通常每年发生一次，并且常常由复杂的环境线索触发。这导致缺乏关于芳香化酶抑制的敏感性和不良反应的测试数据以及不确定性。本研究使用西部食蚊鱼（盖氏食蚊鱼）作为实验室模型，来研究化学性芳香化酶抑制对群体同步卵母细胞发育的不利影响。成年雌性西部食蚊鱼在一个完整的生殖周期内暴露于0、2或30μg/L的非甾体类芳香化酶抑制模型化学物质法倔唑中。在代表卵黄发生前期静止、早期卵黄发生、晚期卵黄发生/早期卵巢再发育以及晚期卵巢再发育的四个时间点对鱼进行采样。测量了众多生殖参数的时间变化，包括性腺体指数（GSI）、血浆性类固醇以及大脑、肝脏和性腺中对生殖重要的选定基因的表达。与对照处理的鱼相比，暴露于2和30μg/L法倔唑的鱼卵巢中cyp19表达持续升高，肝脏中vtg表达降低，且GSI较低。这些反应表明，在法倔唑处理的鱼的试验期间，群体同步生殖周期的完成并不成功。这些不良反应数据表明，接触芳香化酶抑制剂有可能在具有异步和群体同步生殖策略的广泛鱼类中导致生殖功能障碍。
