Doctoral Dissertation Research: Developmental programming and epigenetic changes in response to maternal environments

博士论文研究：响应母体环境的发育规划和表观遗传变化

• 批准号: 1825469
• 负责人: Alicia Smith
• 金额: $ 3.12万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1825469&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Developmental; programming

Developmental programming refers to early life biological responses to the environment that can shape long-term well-being. The prenatal period is a critical window for developmental programming, with a variety of environmental signals being transmitted from a mother to her offspring, potentially reflected as "epigenetic" changes in offspring gene regulation. This dissertation project will advance our understanding of epigenetic mechanisms of adaptation by identifying correlations in gene regulation between a mother and her offspring and investigating the impact of acute and chronic maternal stressors on infant DNA methylation. The project will create STEM training opportunities in epigenetic research for undergraduate and graduate students. Results from this study will contribute to biocultural research on life history and social determinants of well-being, including for understudied populations, and will have the potential to inform clinical policy and practice. Findings will be disseminated to study participants and the general public through various venues, including prenatal care groups.Developmental programming begins before birth, meaning that the experience of the mother is critical for offspring adaptability and fitness. Maternal signals transmitted to the offspring prenatally may represent the mother's total life history and/or the acute environment, including experiences of stress. One mechanism through which the offspring can respond to these signals is through epigenetic modifications, including changes in DNA methylation. The investigators will use infant DNA methylation at birth as a sensor of the prenatal environment, to assess how the offspring adapts to various maternal signals relayed during pregnancy. They will address whether infant methylation is more correlated with maternal methylation at 7-15 weeks, reflecting the cumulative life history of the mother before pregnancy as DNA methylation changes over the life course in response to the environment, or at 23-34 weeks, where maternal DNA methylation would be expected to change in response to the pregnancy-specific environment. A collection of DNA methylation marks that represent an "epigenetic clock" of chronological age will be used as a summary measure of life history in the mother and developmental maturity in the neonate.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.

发育规划是指生命早期对环境的生物反应，可以塑造长期的福祉。产前时期是发育编程的关键窗口，各种环境信号从母亲传递给她的后代，可能反映为后代基因调控的“表观遗传”变化。本论文项目将通过识别母亲和她的后代之间的基因调控相关性，并调查急性和慢性母体压力对婴儿DNA甲基化的影响，来促进我们对适应的表观遗传机制的理解。该项目将为本科生和研究生创造表观遗传学研究的STEM培训机会。这项研究的结果将有助于对生活史和幸福的社会决定因素的生物文化研究，包括研究不足的人群，并将有可能为临床政策和实践提供信息。研究结果将通过包括产前护理小组在内的各种渠道传播给研究参与者和公众。发育规划在出生前就开始了，这意味着母亲的经历对后代的适应性和健康至关重要。母亲产前传递给后代的信号可能代表母亲的全部生活史和/或急性环境，包括压力的经历。后代可以对这些信号做出反应的一种机制是通过表观遗传修饰，包括DNA甲基化的变化。研究人员将使用婴儿出生时的DNA甲基化作为产前环境的传感器，以评估后代如何适应怀孕期间传递的各种母体信号。他们将讨论婴儿甲基化是否与母体甲基化在7-15周时更相关，反映了母亲在怀孕前的累积生活史，因为DNA甲基化在生命过程中响应环境而变化，或者在23-34周时，预计母体DNA甲基化会响应妊娠特定环境而变化。一组DNA甲基化标记代表了实际年龄的“表观遗传时钟”，将被用作母亲生活史和新生儿发育成熟度的概括衡量标准。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。