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The role of b-carotene in maternal-fetal nutrition

β-胡萝卜素在母婴营养中的作用

基本信息

批准号：
8737793
负责人：
Loredana Quadro
金额：
$ 31.09万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-02-15 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8737793
关键词：
Address All-Trans-Retinol Biological Birth Blood Blood Circulation Carotene Carotenoids Cell Differentiation process Child Cleaved cell Congenital Abnormality Consumption Data Developed Countries Development Diet Dietary Practices Dose Egg Yolk Embryo Embryonic Development Enzymes Etiology Fetal Death Fetus Growth and Development function Health Homeostasis Human Incidence Intake Knowledge Literature Low Birth Weight Infant Low Density Lipoprotein Receptor Maternal Mortality Metabolism Micronutrients Mothers Mouse Strains Mus Mutation Nutrient Nutritional status Organ Oxygenases Placenta Plants Population Pregnancy Process Provitamin A Carotenoid Public Health Retinoids Retinol Binding Proteins Role SR-B proteins Source Staging Tissues United States Vitamin A Vitamin A Deficiency Vitamins Yolk Sac catalyst cell growth corticosterone methyl oxidase I corticosterone methyl oxidase II dietary supplements embryo tissue fetal fetus nutrition insight lipid metabolism lipoprotein lipase malformation mouse development pi bond uptake

项目摘要

DESCRIPTION (provided by applicant): The nutritional status of the mother is a key factor for the development and growth of the fetus. Vitamin A is an essential nutrient for the developing embryo, which depends on maternal circulating vitamin A (or retinoids) to fulfill its needs. Indeed, embryonic vitamin A-deficiency as well as -excess result in fetal malformations, representing a serious problem in both the developing world and the industrialized countries. Humans rely mainly on provitamin A carotenoids as a source of vitamin A. ¿-carotene is the best-characterized vitamin A precursor and the most abundant supply of this nutrient in the human diet. Two enzymes, ¿-carotene-15, 15'-oxygenase (CMO I) and ¿-carotene-9, 10'-oxygenase (CMO II), have been identified as catalysts for the cleavage of specific double bonds of ¿-carotene, resulting in the formation of vitamin A. At present, the role of ¿-carotene in maternal-fetal nutrition is not well understood. Evidences from the literature suggest that this carotenoid may be an important, localized source of vitamin A for the developing tissues. We plan to address this crucial biological question by using mice lacking both CMO I and retinol-binding protein (RBP), the sole specific carrier for retinol in the circulation. We will also use mice lacking low density lipoprotein receptor (LDLr) or class B scavenger receptor (SR-BI) or lipoprotein lipase (LPL) to investigate the role of these key players of the lipid metabolism in facilitating the maternal-fetal transfer of ¿-carotene. Three specific aims are proposed: (1) To identify factors that modulate the expression of CMO I and CMO II during mouse development. (2) To determine whether ¿-carotene is an alternative source of vitamin A for embryonic synthesis of retinoids. (3) To investigate the mechanisms of uptake and processing of ¿-carotene by the maternal-fetal barrier (i.e., placenta and yolk sac). These studies will ultimately expand our knowledge of maternal-fetal nutrition and dietary contribution to embryonic development, thus providing new insight into appropriate dietary practices during pregnancy. These studies have a significant impact on human health, since they aim at reducing the incidence of fetal malformations associated with an abnormal maternal intake of micronutrients, such as vitamins.

描述（申请人提供）：母亲的营养状况是胎儿发育和生长的关键因素。维生素 A 是发育中胚胎的必需营养素，胚胎依赖母体循环维生素 A（或类视黄醇）来满足其需求。事实上，胚胎维生素A缺乏和过量都会导致胎儿畸形，这在发展中国家和工业化国家都是一个严重的问题。人类主要依靠维生素A原类胡萝卜素作为维生素A的来源。β-胡萝卜素是特性最好的维生素A前体，也是人类饮食中这种营养素供应最丰富的。 Н-胡萝卜素-15, 15'-加氧酶(CMO I)和Ф-胡萝卜素-9, 10'-加氧酶(CMO II)这两种酶已被确定为Ф-胡萝卜素特定双键裂解的催化剂，从而形成维生素A。目前Ф-胡萝卜素在母胎营养中的作用尚不明确。很好理解。文献证据表明，这种类胡萝卜素可能是发育组织中维生素 A 的重要局部来源。我们计划通过使用同时缺乏 CMO I 和视黄醇结合蛋白 (RBP) 的小鼠来解决这个关键的生物学问题，视黄醇结合蛋白是循环中视黄醇的唯一特异性载体。我们还将使用缺乏低密度脂蛋白受体（LDLr）或B类清道夫受体（SR-BI）或脂蛋白脂肪酶（LPL）的小鼠来研究脂质代谢的这些关键参与者在促进β-胡萝卜素母胎转移中的作用。提出了三个具体目标：（1）确定小鼠发育过程中调节 CMO I 和 CMO II 表达的因素。 (2) 确定β-胡萝卜素是否是胚胎合成类维生素A的维生素A的替代来源。 (3) 探讨母胎屏障（即胎盘和卵黄囊）摄取和加工β-胡萝卜素的机制。这些研究最终将扩大我们对母胎营养和饮食对胚胎发育的贡献的了解，从而为怀孕期间适当的饮食习惯提供新的见解。这些研究对人类健康具有重大影响，因为它们的目的是减少与母亲维生素等微量营养素摄入异常相关的胎儿畸形的发生率。