Understanding Placental Adaptation to Maternal Malnutrition

了解胎盘对母亲营养不良的适应

• 批准号: 9134190
• 负责人: Michael Carey Satterfield
• 金额: $ 29.79万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134190
• 关键词: Adult; Angiogenic Factor; Animal Feed; Animal Model; Animals; Arteries; Biological; Biological Markers; Biological Models; Biology; Blood Vessels; Blood flow; Body Size; Breeding; Collaborations; Complex; Development; Diagnostic; Domestic Animals; Embryo; Endothelial Cells; Environment; Exhibits; Female; Fetal Development; Fetal Growth; Fetal Growth Retardation; Fetal Weight; Fetus; Foundations; Gases; Gene Expression; Genes; Genetic; Genotype; Goals; Growth; Health; Hormonal; Hormones; Human; In Vitro; Incidence; Individual; Intervention; Knowledge; Life; Livestock; Malnutrition; Medical; Metabolic; Molecular; Molecular Biology Techniques; Morbidity - disease rate; Mothers; Neonatal Mortality; Newborn Infant; Nutrient; Nutritional Study; Onset of illness; Operative Surgical Procedures; Outcome; Pathway interactions; Physiological; Placenta; Placentation; Play; Population; Pregnancy; Prenatal Nutrition; Production; Reproductive Biology; Research; Research Personnel; Resources; Role; Selection Criteria; Series; Sheep; Small for Gestational Age Infant; Study models; Systems Biology; Testing; Uterus; Weight; Work; amino acid metabolism; angiogenesis; at-risk pregnancies; base; biomarker development; biomarker identification; cost; fetal; fetus nutrition; genetic selection; human subject; innovation; insight; male; maternal nutrient restriction; mortality; multidisciplinary; neonatal morbidity; novel; nutrient metabolism; nutrition related genetics; offspring; pregnant; response; therapeutic development; tool; wasting

 DESCRIPTION (provided by applicant): In domestic animals and humans, optimal fetal growth is predicated on sufficient nutrient delivery across the placenta. Our long-range goal is to discover and understand the hormonal, cellular, and molecular mechanisms regulating placental growth and function to support optimal fetal growth. Importantly, impaired fetal growth is associated with increased incidence of neonatal morbidity and mortality in both livestock species and humans. In addition, emerging evidence related to developmental origins of adult-onset disease highlight the additional long- term consequences of a poor uterine environment on lifelong health. The goal of this proposal is to capitalize on natural population variance using the sheep, (serving as both an agriculturally important food animal as well as an accepted biomedical model for studies related to humans) to elucidate the mechanisms by which the placenta can adapt to maternal malnutrition to support varying degrees of fetal growth. To achieve this goal we will conduct a series of nutritional studies using singleton pregnant ewes of similar body size and condition, carrying embryos generated from similar males and superovulated donor females. We have previously employed this strategy and observed increased variance in levels of fetal growth in nutrient restricted ewes. We will capitalize on thi natural population variance by comparing the upper and lower quartiles of individuals based upon fetal growth to elucidate mechanisms controlling placental growth and function. Specific aims are to: 1) elucidate the relative contributions of fetal genotype and the host uterine environment on fetal development; 2) investigate mechanisms governing placental vascular growth and function in nutrient-restricted ewes; and 3) identify the contribution of select nutriens in regulating placental growth and function in nutrient-restricted ewes. This research is innovative because it will develop a unique animal model for the study of placental growth, function, and adaptation. In addition, we will employ novel surgical strategies allowing for retrospective analysis of early placental gene expression based on rates of fetal growth in late gestation. Completion of the proposed research is expected to fill a critical gap in our existing knowledge by providing novel insights into placental growth and function as they relate to the spectrum of observed rates of fetal growth. Translational outcomes of the proposed research include biomarkers for placental function as well as the identification of novel nutritional and genetic targets for the development of therapeutic strategies to enhance fetal growth in undernourished mothers.

 描述（由适用提供）：在家畜和人类中，预测整个胎盘足够的营养递送的最佳胎儿生长。我们的远程目标是 发现并理解调节位置生长和功能以支持最佳胎儿生长的马，细胞和分子机制。重要的是，受损的胎儿生长与牲畜和人类的新生儿发病率和死亡率的发生率增加有关。此外，与成年疾病的发育起源有关的新兴证据突出了子宫环境不良环境对终生健康的额外长期后果。该提案的目的是利用自然人口差异 绵羊（既是重要的食物动物，也是与人类有关的研究的公认生物医学模型），以阐明plopeta可以适应母体营养不良以支持不同程度的胎儿生长的机制。为了实现这一目标，我们将使用具有相似体型和状况的Singleton怀孕母羊进行一系列营养研究，该母羊携带由类似雄性和超额供体雌性产生的胚胎。我们以前已经采用了这种策略，并观察到养分受限母羊的胎儿生长水平的差异增加。我们将通过比较基于胎儿生长的上下四分位数来利用自然人口差异，以阐明控制占地生长和功能的机制。具体目的是：1）阐明胎儿基因型和子宫环境对胎儿发育的相对贡献； 2）研究有关占地血管生长和营养限制母羊功能的机制； 3）确定精选营养师在确定营养素限制母羊中的位置生长和功能方面的贡献。这项研究具有创新性，因为它将开发出一种独特的动物模型来研究占地生长，功能和适应性。此外，我们将采用新型的手术策略，以基于妊娠晚期胎儿生长速率来回顾性分析。预计拟议研究的完成将通过与观察到的胎儿生长速率相关的斑点生长和功能的新见解，从而填补我们现有知识的关键空白。拟议的研究的转化结果包括用于占位术功能的生物标志物，以及鉴定出新的营养和遗传靶标，以发展治疗策略，以增强母亲不足的母亲的胎儿生长。