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

人类已经进化到对他们生长和发育的环境有生物反应。一个越来越受关注的环境是子宫内环境，因为这代表了胎儿生物学直接受母体生物学影响的时期，而母体生物学本身又由女性一生的经历塑造。有趣的是，怀孕期间压力激素水平较高的女性往往会生下压力生理改变的婴儿，并增加日后患疾病的风险。虽然这些关联现在已经在一些人群中被记录下来，但对塑造压力生理学的母体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。（西北大学），在克里斯托弗·久泽博士的指导下，解决了以下目标：1）确定母亲社会环境的哪些方面与怀孕期间的压力激素有关; 2）评估母亲的应激激素是否能预测婴儿期后代的应激生理学; 3）调查后代表观遗传标记的变化是否对应激生理学的代际传递负责，表观遗传标记改变了基因表达模式。 数据将来自新西兰奥克兰的社会经济和种族多样的孕妇样本，该项目的研究结果将有助于澄清婴儿是否遗传了母亲压力经历的生物学但非基因组印记。因此，它将为我们理解社会内部的不平等如何影响社会压力因素的暴露，如何影响几代人之间的生物学和健康差异做出重要贡献。此外，该项目还支持一名代表性不足的少数民族女研究生的培训和专业发展。共同参与者组织了针对新西兰当地助产士、产科医生和公共卫生从业人员的外联活动，以报告对这些专业人员及其人口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.