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，这些不平等背后的生物机制仍然知之甚少。描述性流行病学研究发现，宫内环境和出生后早期环境在代际传播健康差异方面发挥了作用。这篇论文由博士生Amanda Mummert(在Emory大学Michelle Lampl博士的指导下)研究了特定的慢性心理社会压力和营养不良的暴露是否会对胎儿和婴儿的骨骼生长和身体成分产生代际影响。这项研究的主要假设是，胎儿和婴儿暴露在慢性应激和高热量食物中将导致骨骼生长和骨密度明显不足，以及在婴儿时期肥胖增加和脂联素产生减少。在人类身上进行这项研究的挑战包括我们的繁殖期很长，以及拟议的研究计划的侵入性，这些问题可以通过在人类健康的转换模型中检验这一假设来克服。因此，这项研究使用了一个合适的灵长类动物模型，即耶克斯国家灵长类研究中心的56对猕猴母婴样本。在母亲和婴儿出生90天和150天，以及出生后3个月和6个月时，将对母亲和婴儿进行超声波检查、双能X射线吸收测量、人体测量学和生物标志物分析。这些生物学评估将伴随着行为观察，以记录类似应激样行为的发生和母婴护理互动。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不断量化，自动喂食器根据微芯片信号分配食物。通过揭示先天生理是如何受到健康的两个主要社会决定因素--营养和慢性压力--的影响，这项研究有助于2020年健康人的优先事项，以更好地表征环境和生物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的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”并影响人类健康的，特别是在慢性病发病率和医疗保健成本持续上升的情况下。特别是，这项研究预计将揭示目前尚不清楚的导致长期健康不平等的生物机制，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记物。

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.