EAPSI:Characterizing Estrogen-Like Activity of Oil Spill Dispersant COREXIT® EC9500A

类固醇激素对脊椎动物的正常功能和生理维持至关重要。具体地说，雌激素通过雌激素受体(ER)在生殖系统的分化和生长中发挥重要作用。拟议的项目检查了Corexit®EC9500A的雌激素样活性，Corexit®EC9500A是获准在2010年BP深水地平线漏油事件中使用的主要分散剂，在小菜蛾和几种鳄鱼中具有类似雌激素的活性。这一结果将有助于理解Corexit的亚致死效应，以及它是否具有环境雌激素的功能。此外，这一结果将有助于开发毒性较低的新型分散剂。利用前哨物种研究环境污染物，包括内分泌干扰污染物(EDCs)的影响是至关重要的，因为EDCs对野生动物和人类的内分泌系统都有潜在的改变。这项研究将与位于日本冈崎的国家基础生物学研究所的著名雌激素类化学物质内分泌干扰和发育影响专家井口泰森博士合作进行。在一些海龟和所有鳄鱼中，雌激素在温度依赖型性别决定(TSD)中发挥着重要作用，在胚胎发育的温度敏感期(TSP)中，孵化温度决定了胚胎的性别。在TSP过程中，单次暴露于外源雌激素会盖过温度的影响，并通过在雄性产生温度下诱导卵巢发育而导致性别反转或性别比例扭曲。表现出TSD的爬行动物物种已被用作研究包括内分泌细胞在内的环境污染物的长期暴露的哨兵物种。通过与核激素受体结合的荧光素酶反式激活实验，Corexit在体外通过密西西比扬子鳄雌激素受体1显示了雌激素样活性。将用这些克隆的内质网进行转录激活分析，以比较不同爬行动物物种之间的转录激活。该NSF EAPSI奖是与日本科学促进会合作资助的。

Steroid hormones are critical for the normal function and maintenance of physiology in vertebrates. Specifically, estrogens play important roles in differentiation and growth of the reproductive system via the estrogen receptor (ER). The proposed project examines estrogen-like activity of COREXIT® EC9500A, the primary dispersant authorized for use in response to the 2010 BP Deepwater Horizon oil spill, in diamondback terrapins and several species of crocodilians. The results will contribute to understanding the sublethal effects of COREXIT and whether it functions as an environmental estrogen. Moreover, the results will help in the development of less toxic, novel dispersants. Investigating the effects of environmental contaminants, including endocrine disrupting contaminants (EDCs), using sentinel species is critical due to the potential alteration of the endocrine system by EDCs in both wildlife species and humans. This research will be conducted in collaboration with Dr. Taisen Iguchi, a renowned expert on endocrine disruption and developmental effects of estrogen-like chemicals, at the National Institute for Basic Biology in Okazaki, Japan. Estrogens play an important role in temperature-dependent sex determination (TSD) in some turtles and all crocodilians in which incubation temperatures during a thermosensitive period (TSP) in embryonic development determine sex of the embryo. A single exposure to exogenous estrogen during TSP overrides the effects of temperature, and leads to sex reversal or skewed sex ratios by inducing ovarian development at a male-producing temperature. Reptile species that exhibit TSD have been used as sentinel species to investigate chronic exposure to environmental contaminants including EDCs. Using luciferase transactivation assays with nuclear hormone receptors, COREXIT demonstrated estrogenic activity in vitro via Alligator mississippiensis estrogen receptor 1. The proposed work aims to clone and characterize ERs from diamondback terrapins and several crocodilian species. Transactivation assays will be performed with these cloned ERs to compare the transactivation among the different reptile species. This NSF EAPSI award is funded in collaboration with the Japan Society for the Promotion of Science.