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。 具体而言，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。 该项目旨在检测COREXIT® EC 9500 A在菱纹龟和几种鳄鱼中的雌激素样活性。COREXIT ® EC 9500 A是被授权用于应对2010年BP深水地平线漏油事件的主要分散剂。 这些结果将有助于了解COREXIT的亚致死效应以及它是否具有环境雌激素的功能。 此外，研究结果将有助于开发毒性较小的新型分散剂。 调查环境污染物的影响，包括内分泌干扰物（EDCs），使用哨兵物种是至关重要的，因为内分泌干扰物在野生动物物种和人类的内分泌系统的潜在改变。 这项研究将与日本冈崎国立基础生物学研究所的内分泌干扰和雌激素样化学品对发育影响的著名专家Taisen Iguchi博士合作进行。雌激素在某些海龟和所有鳄鱼的温度依赖性性别决定（TSD）中起着重要作用，其中胚胎发育中的温敏期（TSP）的孵化温度决定了胚胎的性别。 在TSP期间，单一暴露于外源性雌激素可克服温度的影响，并通过在雄性产生温度下诱导卵巢发育而导致性逆转或性别比例偏斜。 表现出TSD的爬行动物物种已被用作哨兵物种，以调查慢性暴露于环境污染物，包括内分泌干扰物。 使用核激素受体的荧光素酶反式激活试验，COREXIT通过Alligator mississippiensis雌激素受体1证明了体外雌激素活性。 这项工作的目的是克隆和表征的ERs从菱纹龟和几个鳄鱼物种。 将对这些克隆的ER进行反式激活试验，以比较不同爬行动物物种之间的反式激活。这个NSF EAPSI奖是与日本科学促进协会合作资助的。

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.