Collaborative Research: Effects of Developmental Hypoxia on Juvenile Cardiac Function

合作研究:发育性缺氧对青少年心脏功能的影响

基本信息

  • 批准号:
    1755282
  • 负责人:
  • 金额:
    $ 16.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-05-15 至 2023-04-30
  • 项目状态:
    已结题

项目摘要

This collaborative project will investigate the outcome of low environmental oxygen levels (hypoxia) experienced during early development on the cardiovascular system of the American alligator, a species that naturally experiences low oxygen during embryonic life. The cardiovascular system is essential for the distribution of oxygen and metabolic fuels to active tissues. In some developing vertebrates, including humans, the function of the immature cardiovascular system can be negatively affected by environmental challenges such as low oxygen, and these changes can adversely affect the health of the adult. By contrast, species that naturally experience low oxygen during development, such as alligators, can benefit later in life from the changes to the cardiovascular system resulting from developmental hypoxia. Cardiovascular function will be assessed in two-year-old juvenile American alligators that were exposed to hypoxia as embryos, under active conditions (while exercising and after feeding). An integrative assessment will be conducted from the level of individual proteins to that of the whole animal. The broader impacts of the project include a significant number of opportunities for training students at multiple education levels in skills relevant to biomedical research, which will have a direct impact on the future work force, and training and practice in communicating science to the public. Developmental plasticity is a phenomenon that enables multiple environmentally mediated phenotypes to be generated from a single genotype. This plasticity, which is present in all multicellular taxa, can result in beneficial or adaptive changes that enhance function during juvenile and adult life. Hypoxia is an ecologically relevant environmental condition that, if encountered during embryonic life when organ systems are developing, can result in altered juvenile phenotypes that can impact organismal performance and affect animal fitness. Despite the important role hypoxia plays in causing phenotypic change, fundamental questions remain regarding the long-term effects of developmental hypoxia in vertebrates. This project investigates the impact of hypoxia experienced during a critical period of development on cardiovascular function of juvenile alligators at multiple levels of biological organization: from whole-animal performance, to functional studies of the cardiovascular system, to the organ, cellular, protein, and gene levels of organization. Alligators will be studied because they can naturally experience hypoxia during development and as adults. This approach will establish links between molecular and cellular traits, including changes in expression of genes involved in calcium dynamics and in cardiomyocyte contractility that underpin differences in cardiac output at the whole organism level. This multi-level approach will provide a comprehensive understanding of how embryonic hypoxia impacts cardiovascular function, with applicability to other vertebrate systems. The research findings will provide basic information that will be needed to make informed animal management decisions in the era of global climate change, and could lead to future treatment options for cardiovascular disease states. The project involves research training of graduate students and undergraduate students recruited from groups under-represented in science, as well as outreach to K-12 students and the general public.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
这一合作项目将调查美国扬子鳄在早期发育过程中经历的低环境氧气水平(低氧)对心血管系统的影响,美洲扬子鳄是一种在胚胎生活中自然经历低氧的物种。心血管系统对于将氧气和代谢燃料分配到活跃的组织是必不可少的。在包括人类在内的一些发育中的脊椎动物中,未成熟心血管系统的功能可能会受到低氧等环境挑战的负面影响,这些变化可能会对成年动物的健康造成不利影响。相比之下,在发育过程中自然经历低氧的物种,如鳄鱼,可以在以后的生活中受益于发育低氧导致的心血管系统变化。将评估两岁大的美国扬子鳄幼崽的心血管功能,这些扬子鳄在活动条件下(运动时和喂食后)在胚胎时期暴露于低氧环境中。将从单个蛋白质水平到整个动物水平进行综合评估。该项目的更广泛影响包括为不同教育水平的学生提供大量培训与生物医学研究有关的技能的机会,这将对未来的劳动力产生直接影响,以及在向公众传播科学方面的培训和实践。发育可塑性是一种现象,能够从单一的基因中产生多种环境介导的表型。这种存在于所有多细胞类群中的可塑性可以导致有益的或适应性的变化,从而增强青少年和成年生命的功能。缺氧是一种与生态相关的环境条件,如果在器官系统发育的胚胎生命期间遇到这种情况,可能会导致幼体表型改变,从而影响组织的表现和动物的健康。尽管低氧在引起表型变化中起着重要作用,但对于脊椎动物发育中低氧的长期影响仍然存在基本问题。本项目从整体动物表现、心血管系统功能研究、器官、细胞、蛋白质和基因组织水平等多个生物组织水平,研究在发育的关键时期所经历的低氧对扬子鳄幼体心血管功能的影响。将对鳄鱼进行研究,因为它们在发育过程中和成年后都会自然经历缺氧。这种方法将在分子和细胞特征之间建立联系,包括涉及钙动力学和心肌细胞收缩能力的基因表达的变化,这是整个生物体水平心输出量差异的基础。这种多层次的方法将提供对胚胎缺氧如何影响心血管功能的全面理解,并适用于其他脊椎动物系统。研究结果将提供在全球气候变化时代做出明智的动物管理决策所需的基本信息,并可能导致未来心血管疾病状态的治疗选择。该项目涉及对从科学中代表性不足的群体招募的研究生和本科生的研究培训,以及对K-12学生和普通公众的推广。该奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Embryonic Temperature Programs Phenotype in Reptiles
胚胎温度决定爬行动物的表型
  • DOI:
    10.3389/fphys.2020.00035
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Singh, Sunil Kumar;Das, Debojyoti;Rhen, Turk
  • 通讯作者:
    Rhen, Turk
Incubation temperature and satiety influence general locomotor and exploratory behaviors in the common snapping turtle (Chelydra serpentina)
  • DOI:
    10.1016/j.physbeh.2020.112875
  • 发表时间:
    2020-06-01
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Miller, Soleille;Derenne, Adam;Rhen, Turk
  • 通讯作者:
    Rhen, Turk
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Turk Rhen其他文献

Cardiovascular responses to putative chemoreceptor stimulation of embryonic common snapping turtles (<em>Chelydra serpentina</em>) chronically incubated in hypoxia (10% O<sub>2</sub>)
  • DOI:
    10.1016/j.cbpa.2021.110977
  • 发表时间:
    2021-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    John Eme;Kevin B. Tate;Turk Rhen;Dane A. Crossley
  • 通讯作者:
    Dane A. Crossley
Characterization of the FoxL2 proximal promoter and coding sequence from the common snapping turtle (<em>Chelydra serpentina</em>)
  • DOI:
    10.1016/j.cbpa.2017.07.003
  • 发表时间:
    2017-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Lei Guo;Turk Rhen
  • 通讯作者:
    Turk Rhen
Atrazine alters expression of reproductive and stress genes in the developing hypothalamus of the snapping turtle, <em>Chelydra serpentina</em>
  • DOI:
    10.1016/j.tox.2016.08.001
  • 发表时间:
    2016-07-29
  • 期刊:
  • 影响因子:
  • 作者:
    Kathryn L.G. Russart;Turk Rhen
  • 通讯作者:
    Turk Rhen

Turk Rhen的其他文献

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{{ truncateString('Turk Rhen', 18)}}的其他基金

Epigenomic Analysis of Temperature-dependent Sex Determination
温度依赖性性别决定的表观基因组分析
  • 批准号:
    1558034
  • 财政年份:
    2016
  • 资助金额:
    $ 16.5万
  • 项目类别:
    Continuing Grant
MRI-R2: Acquisition of a Liquid Handling Robot and a High-throughput Real-time PCR Thermocycler for Genetics and Genomics Research at UND
MRI-R2:UND 采购用于遗传学和基因组学研究的液体处理机器人和高通量实时 PCR 热循环仪
  • 批准号:
    0959369
  • 财政年份:
    2010
  • 资助金额:
    $ 16.5万
  • 项目类别:
    Standard Grant
Genomic and Genetic Analysis of Temperature-dependent Gender Determination
温度依赖性性别决定的基因组和遗传分析
  • 批准号:
    0923300
  • 财政年份:
    2009
  • 资助金额:
    $ 16.5万
  • 项目类别:
    Standard Grant

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