Doctoral Dissertation Improvement: Effects of Social, Behavioral, and Biological Exposures on Fetal and Postnatal Skeletal Growth and Body Composition

反映社会、环境和经济劣势的健康结果的显著差异仍然存在，而这些不平等背后的生物学机制仍然知之甚少。描述性流行病学研究表明，宫内环境和产后早期环境都对健康差异的代际传播起作用。该论文项目由博士生Amanda Mummert（在埃默里大学Michelle Lampl博士的指导下）研究慢性社会心理压力和营养不良的特定暴露是否对胎儿和婴儿的骨骼生长和身体组成有代际影响，这是在表现出健康差异的人群中注意到的基本缺点。该研究的主要假设是，胎儿和婴儿长期暴露于压力和高热量食物中，会导致骨骼生长和骨矿物质密度明显不足，以及婴儿时期肥胖增加和脂联素产生减少。在人类中进行这项研究的挑战包括我们的长生殖期和拟议研究计划的侵入性，通过在人类健康的转化模型中测试这一假设来克服这些挑战。因此，这项研究利用了一种合适的灵长类动物模型，即耶基斯国家灵长类动物研究中心的56只恒河猴（Macaca mulatta）母子对样本。超声检查、双能x线吸收测定、人体测量和生物标志物测定将在90和150胎龄以及出生后3和6个月的母亲和婴儿中重复进行。这些生物学评估将伴随着行为观察，以记录压力样行为和母婴护理互动的发生。此外，通过使用根据微芯片信号分配食物的自动喂食器，将对母亲和断奶婴儿的食物摄入量进行持续量化。通过揭示先天生理如何受到健康、营养和慢性压力这两个主要社会决定因素的影响，本研究有助于“健康人民2020”优先事项更好地表征环境和生物学对人类健康的复杂贡献。虽然传染病仍然是一个重大的公共卫生问题，但全球发病率和死亡率负担深深植根于社会和结构性问题，包括失业和贫穷、缺乏社会支持和慢性压力。当务之急是为了公共卫生规划的目的，调查这些更大的社会因素是如何“深入人心”并影响人类健康的，特别是在慢性病发病率和卫生保健费用持续上升的情况下。特别是，预计这项研究将揭示目前未知的导致长期健康不平等的生物学机制，这些机制可能作为解释公共卫生干预措施有效性的生物标志物。

Significant differences in health outcomes reflecting social, environmental, and economic disadvantages persist and the biological mechanisms underlying these inequalities remain poorly understood. Descriptive epidemiologic studies identify that both intrauterine and early postnatal environments play a role in the transmission of health disparities across generations. This dissertation project by doctoral student Amanda Mummert (under the supervision of Dr. Michelle Lampl, Emory University) examines whether the specific exposures of chronic psychosocial stress and poor nutrition, fundamental disadvantages noted among populations exhibiting health disparities, have intergenerational effects on fetal and infant skeletal growth and body composition.The primary hypothesis of the study is that fetal and infant exposure to chronic stress and high calorie foods will lead to distinct deficiencies in skeletal growth and bone mineral density, as well as increased adiposity and decreased adiponectin production in infancy. Challenges to conducting this research in humans include our long reproductive periods and the invasiveness of the proposed research plan, which are overcome by testing this hypothesis in a translational model of human health. The research therefore utilizes an appropriate primate model, a sample of 56 Rhesus macaque (Macaca mulatta) maternal-infant pairs housed at the Yerkes National Primate Research Center. Ultrasonography, dual-energy X-ray absorptiometry, anthropometrics, and biomarker assays will be repeated on mothers and infants at 90 and 150 gestational days of age, as well as 3 and 6 postnatal months of age. These biological assessments will be accompanied by behavioral observations to document the occurrence of stress-like behaviors and mother-infant nursing interactions. Additionally, food intake for mothers and weaned infants will be continuously quantified through the use of automated feeders that dispense food in response to microchip signals. By exposing how innate physiology is impacted by two primary social determinants of health, nutrition and chronic stress, this research contributes to the Healthy People 2020 priority to better characterize the complex contributions of environment and biology to human health. While infectious disease remains a significant public health issue, the global burden of morbidity and mortality is deeply rooted in social and structural issues, including unemployment and poverty, a lack of social support, and chronic stress. It is imperative to investigate how these larger social factors 'get under the skin' and impact human health for public health planning purposes, particularly as chronic disease rates and health care costs continue to rise. In particular, this research is anticipated to reveal currently unknown biological mechanisms that contribute to long-term health inequalities that may serve as biomarkers for interpreting the effectiveness of public health interventions.