Doctoral Dissertation Improvement: Intergenerational effects of maternal stress in pregnancy: Epigenetic Mechanisms

人类已经进化到能够对其生长和发育的环境做出生物反应。人们越来越感兴趣的一个环境是宫内环境，因为这代表了胎儿生物学直接受到母体生物学影响的时期，而母体生物学本身是由女性一生的经历塑造的。有趣的是，怀孕期间应激激素较高的女性往往会生出应激生理发生改变的婴儿，并且在以后的生活中患疾病的风险也会增加。虽然这些关联现已在许多人群中得到记录，但对塑造应激生理学的母亲环境经历的具体方面以及压力经历代际传递的分子机制仍然知之甚少。为了澄清这些问题，博士生 Zaneta Thayer（西北大学）在 Christopher Kuzawa 博士的指导下进行了这项研究，旨在实现以下目标：1）确定母亲社会环境的哪些方面与怀孕期间的压力激素相关； 2）评估母亲的应激激素是否可以预测其后代在婴儿期的应激生理； 3) 研究后代表观遗传标记的变化（其改变基因表达模式）是否是应激生理学代际传递的原因。 数据将来自生活在新西兰奥克兰的孕妇的社会经济和种族多样化样本。该项目的研究结果将有助于澄清婴儿是否继承了母亲压力经历的生物但非基因组印记。因此，它将为我们理解社会内部的不平等（影响社会压力因素）如何影响代际生物学和健康方面的差异做出重要贡献。此外，该项目还支持代表性不足的少数族裔女研究生的培训和专业发展。联合首席研究员为新西兰当地助产士、产科医生和公共卫生从业人员组织了外展活动，报告对这些专业人员及其人群具有潜在价值的研究结果。

Humans have evolved to be biologically responsive to the environment in which they grow and develop. One environment of increasing interest is the intrauterine environment, since this represents a period when fetal biology is directly influenced by maternal biology, which itself is shaped by a woman's lifetime of experiences. Interestingly, women with higher stress hormones in pregnancy tend to give birth to babies with altered stress physiology and increased risk of developing disease in later life. While these associations have now been documented in a number of populations, the specific aspects of maternal environmental experience that shape stress physiology, as well as the molecular mechanisms that underlie the intergenerational transmission of stress experience, remain poorly understood.In order to clarify these issues, this study by doctoral student Zaneta Thayer (Northwestern University), under the guidance of Dr. Christopher Kuzawa, addresses the following aims: 1) Determine what aspects of maternal social environment are associated with stress hormones during pregnancy; 2) Evaluate whether the mother's stress hormones predict stress physiology in their offspring during infancy; and 3) Investigate whether changes in offspring epigenetic markings, which modify patterns of gene expression, are responsible for the intergenerational transmission of stress physiology. Data will come from a socioeconomically- and ethnically-diverse sample of pregnant women living in Auckland, New Zealand.The findings of this project will help clarify whether infants inherit a biological but non-genomic imprint of maternal stress experience. It thus will make an important contribution to our understanding of how inequalities within society, which shape exposure to social stressors, can shape disparities in biology and health across generations. Additionally, this project supports training and professional development of an underrepresented minority female graduate student. The Co-PI has organized outreach events for local midwives, obstetricians and public health practitioners in New Zealand to report study findings of potential value to these professionals and their populations.