Real-time Assessment of Fatty Acid Transit in the Human Placental Syncytiotrophoblast

人胎盘合体滋养层脂肪酸转运的实时评估

• 批准号: 9271979
• 负责人: KEVIN KOLAHI
• 金额: $ 4.9万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-19 至 2019-05-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9271979
• 关键词: Acyl Coenzyme A; Behavior Disorders; Blood; Blood Circulation; Body mass index; Brain; Cardiovascular system; Clinical; Coenzyme A Ligases; Cognition Disorders; Data; Development; Diabetic mother; Diagnosis; Dietary Intervention; Docosahexaenoic Acids; Endowment; Enzymes; Exhibits; Fatty Acids; Fatty acid glycerol esters; Fetal Development; Fetal Growth; Fetus; Functional disorder; Future; Gestational Diabetes; Glean; Goals; Health; Human; Image; Impaired cognition; Intelligence quotient; Intervention; Investigation; Knowledge; Label; Laboratories; Lead; Life; Ligase; Light; Lipids; Measures; Medium chain fatty acid; Metabolic Diseases; Methods; Microscopy; Molecular; Mothers; Movement; Nervous system structure; Neurobehavioral Manifestations; Organelles; Pathway interactions; Placenta; Plasma; Play; Polyunsaturated Fatty Acids; Pregnancy; Process; Publishing; Reporting; Role; Source; Structure; Syncytiotrophoblast; System; Testing; Third Pregnancy Trimester; Time; Tissues; brain volume; cardiovascular health; cognitive function; diabetic; fatty acid transport; fetal; in vivo; lipid transport; manufacturing process; movement analysis; neonate; offspring; particle; potential biomarker; public health relevance; sex; trophoblast; uptake

 DESCRIPTION (provided by applicant): The placenta transports all of the building blocks required for fetal development. In particular, the placenta selectively transfers vital long chain polyunsaturated fatty acids (LCPUFA) to support the developing human brain and cardiovascular system. Adequate abundance of these specific fatty acids is crucial for normal development. Fetal deficiencies of LCPUFA are associated with compromised cardiovascular health, lower Intelligence Quotients (IQ), and behavioral and cognitive disorders that persist for life. Since the fetus has a negligible capacity to make LCPUFA, the main source is from the maternal circulation; a fetal deficiency of LCPUFA can arise from inadequate maternal levels or dysfunctional placental transport. In gestational diabetes, the mother's blood content of LCPUFA is normal but the placenta transfers significantly less LCPUFA, leading to subnormal levels in the fetus. The consequences of this are significant and these offspring display cognitive impairments and symptoms in accordance with LCPUFA deficiency. The mechanisms that underlie the dysregulation of LCPUFA transport in these placentas are poorly understood, especially in light of the fact that lipid transport even in normal pregnancies has been understudied. The goal of this project is to determine how the human placenta transports LCPUFA, first as it occurs in normal pregnancy and then to apply the knowledge gleaned to explain how this process is dysfunctional in mothers who have gestational diabetes. The process of LCPUFA transport has remained elusive because a method to track LCPUFA in real-time in the human placental tissue has not previously existed. This project proposes to live-track fluorescently tagged LCPUFA in human term placenta explants using state-of-the-art microscopy to identify the cellular mechanisms that underlie maternal-fetal LCPUFA transfer. It will first examine this process in placentas from normal, uncomplicated pregnancies. It will additionally examine how LCPUFA handling differs in placentas from mothers who are diagnosed with gestational diabetes. This study can lead to further investigations of potential biomarkers to evaluate dysfunctional placental LCPUFA transfer in vivo and may also help identify targets for strategizing molecular or nutritional interventions to support normal placenta LCPUFA transfer in pregnancies complicated by metabolic disease.

 描述（由申请人提供）：胎盘运输胎儿发育所需的所有构件。特别是，胎盘选择性地转移重要的长链多不饱和脂肪酸（LCPUFA），以支持人类大脑和心血管系统的发育。充足的这些特定脂肪酸对正常发育至关重要。胎儿缺乏LCPUFA与心血管健康受损、智商（IQ）降低以及终身存在的行为和认知障碍有关。由于胎儿产生LCPUFA的能力可以忽略不计，主要来源是母体循环;胎儿LCPUFA缺乏可能是由于母体水平不足或胎盘运输功能障碍。在妊娠糖尿病中，母亲血液中的LCPUFA含量是正常的，但胎盘转移的LCPUFA明显减少，导致胎儿的LCPUFA水平低于正常水平。这一结果是显著的，这些后代表现出认知能力， 根据LCPUFA缺乏症的损害和症状。这些胎盘中LCPUFA转运失调的机制尚不清楚，特别是考虑到即使在正常妊娠中脂质转运也未得到充分研究。该项目的目标是确定人类胎盘如何转运LCPUFA，首先是在正常妊娠中发生，然后应用所收集的知识来解释这一过程如何在患有妊娠糖尿病的母亲中功能失调。LCPUFA的转运过程仍然难以捉摸，因为以前没有一种方法可以实时跟踪人类胎盘组织中的LCPUFA。该项目建议使用最先进的显微镜在人类足月胎盘外植体中实时跟踪荧光标记的LCPUFA，以确定母胎LCPUFA转移的细胞机制。它将首先在正常、无并发症的妊娠胎盘中检查这一过程。它还将研究LCPUFA处理在胎盘中与诊断为妊娠期糖尿病的母亲的不同之处。这项研究可以进一步研究潜在的生物标志物，以评估体内功能障碍的胎盘LCPUFA转移，也可以帮助确定战略分子或营养干预的目标，以支持妊娠合并代谢疾病的正常胎盘LCPUFA转移。