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

发育规划指的是生命早期对环境的生物反应，这种反应可以塑造长期的健康。产前期是发育编程的关键窗口期，各种环境信号从母亲传递给后代，可能反映为后代基因调控的“表观遗传”变化。本论文项目将通过确定母亲和后代之间基因调控的相关性，以及研究急性和慢性母亲应激源对婴儿DNA甲基化的影响，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在表观遗传学研究方面创造STEM培训机会。这项研究的结果将有助于生活史和福祉的社会决定因素的生物文化研究，包括对未充分研究的人群，并将有可能为临床政策和实践提供信息。调查结果将通过包括产前护理小组在内的各种场所向研究参与者和一般公众传播。发育计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适应性至关重要。产前传递给后代的母体信号可能代表母亲的整个生活史和/或急性环境，包括压力经历。后代对这些信号作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。他们将研究婴儿甲基化是否在7-15周时与母体甲基化更相关，这反映了母亲在怀孕前的累积生活史，因为DNA甲基化在整个生命过程中随着环境的变化而变化，或者在23-34周时，母体DNA甲基化预计会随着怀孕特定环境的变化而变化。代表实足年龄的“表观遗传时钟”的DNA甲基化标记的集合将被用作母亲生活史和新生儿发育成熟度的总结测量。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.