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

反映社会、环境和经济不利因素的健康结果的重大差异仍然存在，这些不平等现象背后的生物机制仍然知之甚少。描述性流行病学研究表明，宫内和产后早期环境在几代人之间传播健康差异方面发挥了作用。博士生阿曼达·穆默特的论文项目（在埃默里大学Michelle Lampl博士的监督下）研究了慢性心理社会压力和营养不良的具体暴露，以及表现出健康差异的人群中注意到的基本劣势，对胎儿和婴儿的骨骼生长和身体成分有代际影响。本研究的主要假设是胎儿和婴儿接触慢性压力和高热量食物将导致骨骼生长和骨矿物质密度明显不足，以及婴儿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生殖期长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，这项研究利用了一个适当的灵长类动物模型，一个由56只恒河猴（Macaca mulatta）母婴对组成的样本，该样本被安置在耶基斯国家灵长类动物研究中心。将对妊娠90天和150天以及出生后3个月和6个月的母亲和婴儿重复进行超声检查、双能X线吸收测定法、人体测量学和生物标志物测定。这些生物学评估将伴随行为观察，以记录压力样行为和母婴护理相互作用的发生。此外，母亲和断奶婴儿的食物摄入量将通过使用自动喂食器连续量化，自动喂食器根据微芯片信号分配食物。通过揭示先天生理学如何受到健康、营养和慢性压力这两个主要社会决定因素的影响，这项研究有助于实现2020年健康人的优先目标，更好地描述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，但发病率和死亡率的全球负担深深植根于社会和结构性问题，包括失业和贫困、缺乏社会支持和长期压力。为了公共卫生规划的目的，必须调查这些更大的社会因素是如何“深入皮肤”并影响人类健康的，特别是在慢性病发病率和医疗保健费用持续上升的情况下。特别是，这项研究预计将揭示目前未知的生物机制，有助于长期的健康不平等，可能作为生物标志物解释公共卫生干预措施的有效性。

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.