CAREER: Modulation of a Neuroendocrine System by Endocrine Disruptors - BPA effects on GnRH neuron development, physiology and reproductive behavior in teleost fish

脑内释放促性腺激素释放激素(GnRH)的神经元是包括人类在内的大多数脊椎动物生殖和生殖行为的主要控制器。生殖健康、生育和行为问题被认为与GnRH神经系统的异常发育和功能有关。越来越多的证据表明，内分泌干扰物，如双酚A(BPA)--我们环境中的一种合成雌激素--对许多物种的生殖系统和行为有有害影响。这项研究阐述了长期暴露于低水平的双酚A是如何改变促性腺激素释放激素神经元的发育、生理和生殖行为的。该项目将使用转基因FISH模型，用绿色荧光蛋白标记GnRH神经元，以研究慢性BPA暴露对以下方面的影响：a)胚胎GnRH神经元发育，b)成年GnRH神经元的生理，以及c)交配和社会行为。实验将使用神经电记录、共聚焦成像、免疫组织化学和行为观察。该项目将有助于了解内分泌干扰物如何调节促性腺激素释放激素系统，并为卵巢功能障碍、流产、早产、性早熟和卡尔曼综合征等生殖问题提出潜在的解决方案。这项研究将首次探讨双酚A对促性腺激素释放激素神经元发育、生理和功能的影响，并结合整个动物行为。这项研究的数据和方案将通过普吉特湾大学的档案和实验室网站(http://sidslab.wikispaces.com/).)向学术界和公众提供本科生研究人员将接受细胞、回路和整个动物层面的广泛神经科学培训，并从生态角度进行培训。K-12年级的学生将通过在公立学校的外联，参加密集的讲习班、持续的合作观察研究和定期研讨会。该计划旨在激励、教育和参与，让参与者对科学感到兴奋，对神经科学和环境毒素的影响进行教育，并与社区和环境接触。

Neurons releasing Gonadotropin releasing hormone (GnRH) in the brain are the main controllers of reproduction and reproductive behavior in most vertebrates, including humans. Reproductive health, fertility and behavioral problems have been linked to abnormal development and function of the GnRH neuronal system. There is increasing evidence that endocrine disrupting chemicals, such as bisphenol A (BPA) - a synthetic estrogen in our environment - have deleterious effects on the reproductive systems and behaviors in many species. This study addresses how GnRH neuron development, physiology and reproductive behavior, are altered by chronic exposure to low levels of BPA. This project will use transgenic fish models, having GnRH neurons tagged with green fluorescent proteins, to address effects of chronic BPA exposure on: a) embryonic GnRH neuron development, b) physiology of adult GnRH neurons, and c) mating and social behavior. Experiments will use neural electrical recordings, confocal imaging, immunohistochemistry and behavioral observations. The project will result in understanding how endocrine disruptors modulate the GnRH system and suggest potential solutions for reproductive problems like ovarian dysfunction, miscarriages, pre-term births, precocious puberty and Kallman's syndrome. This study will be the first to address the impact of BPA on GnRH neuron development, physiology, and function, in conjunction with whole animal behavior. Data and protocols from the study will be available to the academic community and the general public via the University of Puget Sound archives and the lab website (http://sidslab.wikispaces.com/). Undergraduate researchers will receive broad neuroscience training at the cell, circuit, and whole-animal levels, with ecological perspectives. K-12 students will be involved in intensive workshops, ongoing collaborative observational studies and regular seminars through outreach at public schools. The plan is to Excite, Educate, Engage by making participants excited about science, educated about neuroscience and the impact of environmental toxins, and engaged with the community and the environment.