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

职业：内分泌干扰物对神经内分泌系统的调节 - BPA 对硬骨鱼 GnRH 神经元发育、生理和繁殖行为的影响

• 批准号: 1253126
• 负责人: Siddharth Ramakrishnan
• 金额: $ 70万
• 依托单位: University of Puget Sound
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1253126&HistoricalAwards=false
• 关键词: CAREER; Modulation; Neuroendocrine; System; Endocrine

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.

脑中释放促性腺激素释放激素（GnRH）的神经元是大多数脊椎动物（包括人类）生殖和生殖行为的主要控制者。生殖健康、生育和行为问题与GnRH神经系统的异常发育和功能有关。越来越多的证据表明，内分泌干扰化学品，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产生有害影响。这项研究讨论了GnRH神经元发育，生理和生殖行为如何通过长期暴露于低水平BPA而改变。 该项目将使用转基因鱼模型，具有标记有绿色荧光蛋白的GnRH神经元，以解决慢性BPA暴露对以下方面的影响：a）胚胎GnRH神经元发育，B）成年GnRH神经元的生理学，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。该项目将导致了解内分泌干扰物如何调节GnRH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。这项研究将是第一个解决BPA对GnRH神经元发育，生理和功能以及整个动物行为的影响。该研究的数据和协议将通过普吉特海湾大学档案馆和实验室网站（http：//sidslab.wikispaces.com/）向学术界和公众提供。本科研究人员将在细胞，电路和整个动物水平上接受广泛的神经科学培训，并具有生态学观点。K-12学生将参与密集的研讨会，正在进行的合作观察研究和定期研讨会，通过在公立学校推广。该计划是通过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，并与社区和环境进行接触来激发，教育，参与。