Environmental Sex Determination and Endocrine Disruption

两种明显而现实的环境影响正在影响着所有的生命形式：气候变化和人为化学污染。事实证明，红耳滑龟胚胎是一个特殊的模型系统，可以评估这些环境因素中的每一个因素的作用以及它们可能如何相互作用。这个物种的性别决定依赖于温度；也就是说，温度(和激素)在一个狭窄的发育窗口中起作用，决定个体的性别。这项研究将揭示温度信号是如何转换到分子开关中的，从而产生卵巢或睾丸。它还将评估胚胎对人为环境化合物的敏感性，这些化合物统称为内分泌干扰物(EDCs)，可导致正常类固醇微环境的破坏，导致发育和生殖异常。这项研究整合了这两个领域的研究，重点是物理和化学环境如何改变性腺决定和性别分化的分子和细胞发育途径。先前由美国国家科学基金会资助的研究证实，两种不同的基因“盒”都参与了这两个过程。这些盒是一组功能相关的基因，它们以特定的方式相互作用，在细胞或组织水平上导致结果。在这种情况下，第一盒是由调节所有脊椎动物性腺分化的性腺决定基因的保守核心组成的。第二盒由编码产生类固醇激素(类固醇生成酶)和感觉(激素受体)的分子的基因组成。了解这些磁带是如何参与的，它们在时间和空间上是如何相互作用的，以及每个磁带内的基因在正常条件下以及暴露在内分泌细胞后是如何相互作用的，这是该项目的长期目标。该研究项目将为培养研究生和本科生提供跨学科的研究机会。地区性辅导活动将侧重于来自代表性不足群体的本科生。生成的序列数据将保存在GenBank中。

Two clear and present environmental impacts are affecting all life forms: climate change and anthropogenic chemical contamination. The red-eared slider turtle embryo has proven to be an exceptional model system to evaluate the role of each of these environmental factors and how they may interact. This species has temperature-dependent sex determination; that is, temperature (and hormones) acting during a narrow window of development, determine the sex of the individual. This research will reveal how the temperature signal is transduced into a molecular switch that results in an ovary or a testis. It will also evaluate the susceptibility of the embryo to anthropogenic environmental compounds, collectively known as endocrine disrupting chemicals (EDCs), which can cause disruptions in the normal steroid microenvironment causing developmental and reproductive abnormalities. This research integrates both areas of research and focuses on how the physical and chemical environments modify the molecular and cellular developmental pathways underlying gonad determination and sexual differentiation. Prior NSF-supported research established that two different "cassettes" of genes are involved in both processes. These cassettes are groups of functionally related genes that interact in a particular manner to cause an outcome at the cellular or tissue level. In this instance the first cassette is composed of a conserved core of gonad-determining genes that regulate gonadal differentiation in all vertebrates. The second cassette consists of the genes that code for the molecules that produce (steroidogenic enzymes) and sense (hormone receptors) steroid hormones. Understanding how these cassettes are engaged, how they interact with one another both temporally and spatially, and how the genes within each cassette interact under normal conditions as well as after exposure to EDCs are the long-term goals of this project. The research program will provide interdisciplinary research opportunities for training graduate and undergraduate students. Regional mentoring activities will focus on undergraduate students from underrepresented groups. Sequence data generated will be deposited in GenBank.