Early environments, epigenetics, and inflammation during pregnancy

怀孕期间的早期环境、表观遗传学和炎症

基本信息

  • 批准号:
    1440564
  • 负责人:
  • 金额:
    $ 28.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-01 至 2018-08-31
  • 项目状态:
    已结题

项目摘要

Environments early in life, during critical periods of development, have lasting effects on human biology. It is well established that nutritional and microbial environments in infancy shape the development and function of the human immune system, but the long term effects of early environments on the regulation of inflammation are not known. Inflammation is important because acute inflammatory responses provide protection against infection, but chronic or dysregulated inflammatory responses contribute to diseases that represent major public health burdens in the US, including cardiovascular disease, diabetes, and adverse pregnancy outcomes like low birth weight and preterm delivery. Scientists also have discovered that epigenetic processes - chemical modifications to genes that have enduring effects on their activity - are important biological mechanisms through which adults 'remember' the environments they experienced early in life. By taking advantage of a unique longitudinal birth cohort study in the Philippines, with more than 30 years of prospective data, this project will contribute to scientific understandings of how environments in infancy can influence the regulation of inflammation in adulthood.The project focuses on pregnant women, since inflammation is activated as part of normal pregnancy, but dysregulated inflammation contributes to preterm labor and delivery and fetal growth restriction. The research tests the hypothesis that undernutrition in infancy (prenatally and postnatally), and low levels of exposure to common microbes (e.g., bacteria in soil, untreated water), contribute to elevated levels of inflammation during pregnancy. It also tests the hypothesis that elevated inflammation during pregnancy leads to adverse birth outcomes (preterm delivery, lower birth weight). Lastly, the project investigates methylation of inflammatory genes - an epigenetic process that modifies gene expression - as a biological mechanism linking early environments, inflammation, and birth outcomes. Data and samples come from an ongoing birth cohort study in the Philippines that has followed the same individuals since their mothers were pregnant with them in 1983-84. The dataset is unique in having the time depth, range of measures, and environmental variation necessary to test the project's hypotheses. Results will shed new light on the developmental processes that contribute to chronic inflammation, with potential implications for well-being of the next generation. In addition, the focus on epigenetics in relation to the social and physical contexts of development will encourage a reconceptualization of the human genome as a dynamic substrate that incorporates information from the environment to alter its structure and function.
生命早期和发育关键时期的环境对人类生物学具有持久影响。众所周知,婴儿期的营养和微生物环境影响人类免疫系统的发育和功能,但早期环境对炎症调节的长期影响尚不清楚。炎症很重要,因为急性炎症反应可以提供针对感染的保护,但慢性或失调的炎症反应会导致美国主要公共卫生负担的疾病,包括心血管疾病、糖尿病以及低出生体重和早产等不良妊娠结局。科学家还发现,表观遗传过程(对基因的化学修饰对其活动产生持久影响)是重要的生物机制,成年人通过它“记住”他们早年经历的环境。通过利用菲律宾独特的纵向出生队列研究以及超过 30 年的前瞻性数据,该项目将有助于科学理解婴儿期的环境如何影响成年期的炎症调节。该项目重点关注孕妇,因为炎症是正常妊娠的一部分,但炎症失调会导致早产和分娩以及胎儿生长受限。该研究检验了这样的假设:婴儿期(产前和产后)营养不良以及接触常见微生物(例如土壤中的细菌、未经处理的水)的水平较低,会导致怀孕期间炎症水平升高。它还检验了这样的假设:怀孕期间炎症加剧会导致不良的出生结果(早产、出生体重降低)。最后,该项目研究了炎症基因的甲基化(一种改变基因表达的表观遗传过程)作为连接早期环境、炎症和出生结果的生物机制。数据和样本来自菲律宾正在进行的一项出生队列研究,该研究自 1983-84 年母亲怀上这些人以来一直对这些人进行追踪。该数据集的独特之处在于具有测试项目假设所需的时间深度、测量范围和环境变化。结果将为导致慢性炎症的发育过程提供新的线索,对下一代的福祉具有潜在影响。此外,对与发展的社会和物理背景相关的表观遗传学的关注将鼓励将人类基因组重新概念化为动态基质,结合来自环境的信息来改变其结构和功能。

项目成果

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Thomas McDade其他文献

Thomas McDade的其他文献

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{{ truncateString('Thomas McDade', 18)}}的其他基金

RAPID: Next phase serological testing for SARS-CoV-2 for biocultural research
RAPID:用于生物文化研究的 SARS-CoV-2 下一阶段血清学检测
  • 批准号:
    2035114
  • 财政年份:
    2020
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
Doctoral Dissertation Research: Investigating the social and developmental determinants of vitamin D production
博士论文研究:调查维生素 D 产生的社会和发展决定因素
  • 批准号:
    1848357
  • 财政年份:
    2019
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
Doctoral Dissertation Research: Cultural and Social Dimensions of Anti-Mullerian Hormone Screening Technologies
博士论文研究:抗苗勒氏管激素筛查技术的文化和社会维度
  • 批准号:
    1823543
  • 财政年份:
    2018
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
Ecology of inflammation in lowland Bolivia
玻利维亚低地炎症生态学
  • 批准号:
    1027687
  • 财政年份:
    2010
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
Doctoral Dissertation Improvement: Market Integration, Stress, and Child Health among the Tsimane' of the Bolivian Amazon
博士论文改进:玻利维亚亚马逊提斯曼人的市场一体化、压力和儿童健康
  • 批准号:
    0622576
  • 财政年份:
    2006
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
Doctoral Dissertation Research: Social Status and Stress among African American Adolescents
博士论文研究:非裔美国青少年的社会地位和压力
  • 批准号:
    0514731
  • 财政年份:
    2005
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
Multidimensional Analysis of Quality of Life
生活质量多维分析
  • 批准号:
    0322380
  • 财政年份:
    2003
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Standard Grant
PECASE: Acculturation, Health, and the Ecology of Immune Function: Integrated Research and Education in Human Population Biology
PECASE:文化适应、健康和免疫功能生态学:人类群体生物学的综合研究和教育
  • 批准号:
    0134225
  • 财政年份:
    2002
  • 资助金额:
    $ 28.42万
  • 项目类别:
    Continuing Grant

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宫内不良环境致子代心血管损伤的表观遗传学机制研究
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    $ 28.42万
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    Continuing Grant
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