Doctoral Dissertation Improvement: In Utero Sources of Skeletal Variation: the Role of Maternal Prenatal Stress

骨骼变异是遗传和非遗传因素共同作用的结果。一些非遗传因素，包括机械负荷、饮食和衰老，已经并将继续被研究。然而，影响早期骨骼发育的因素，特别是产前，并没有得到太多的关注。本项目研究妊娠期间母亲压力作为一种非遗传因素，可能影响胎儿骨骼形成和生长，并在成年后导致骨骼变异。该研究假设，怀孕期间诱发的压力对后代的骨骼发育有显著的负面影响，即使后代的骨骼发育不正常。美国的环境没有压力。在一个对照试验中，怀孕大鼠将在妊娠期间的不同时间受到固定应激。后代将在出生后发育的特定阶段被牺牲。骨质量的测量将从股骨组织学切片中进行，以测试压力母亲和非压力母亲的后代之间的差异。这个项目调查了一个未被充分研究的非遗传因素，可以影响产前骨骼发育，母亲的压力。骨骼发育的这一阶段至关重要，因为任何结构或生化上的损害都可能是不可逆转的。模型生物，大鼠，通常用于骨发育研究。因此，本研究的结果将很容易与其他研究进行比较。智力优势：该项目将有助于澄清一些影响骨质量和微观结构的非遗传因素。鉴于产前压力可能对骨骼表型产生潜在的重大影响，并且大鼠是一种已建立的模型，本研究的意义具有广泛的科学和社会意义。更广泛的影响：本研究是一位来自肯尼亚的非洲妇女的博士论文项目。她是家里第一个上大学的人。该项目将促进国际科学培训和来自代表性不足群体的妇女的教育。

Skeletal variation results from both genetic and non-genetic factors. Some of the non-genetic factors that have been, and continue to be studied include mechanical loading, diet and aging. However, factors that influence early skeletal development, especially prenatally, have not received much attention. This project investigates maternal stress during pregnancy as a nongenetic factor that may affect fetal bone formation and growth, and later lead to skeletal variation observed in adults.The study hypothesizes that induced stress during pregnancy has a significant and negative impact on the skeletal development of offspring, even though the offspring?s environment is stress-free. For a controlled test, pregnant rats will be subjected to immobilization stress at various times during gestation. The offspring will be sacrificed at specific stages of post-natal development. Measurements of bone quality will be taken from femoral histological sections to test for differences between the offspring from stressed and un-stressed mothers.This project investigates an understudied non-genetic factor that can impact prenatal skeletal development, maternal stress. This stage in skeletal development is critical because any structural or biochemical compromise may be irreversible. The model organism, the rat, is commonly used in bone developmental research. Therefore, results from this research will be readily comparable to other studies.Intellectual Merit: This project will help to clarify some of the non-genetic factors that influence bone quality and microstructure. Given the potentially significant impact that prenatal stress can have on skeletal phenotypes, and that rats are an established model, implications from this research are of broad scientific and social relevance.Broader Impacts: This research is the doctoral dissertation project of an African woman from Kenya. She is the first in her family to attend college. This project will promote international science training and the education of a woman from an underrepresented group.