Iron physiology and pathology in pregnancy
妊娠期铁的生理学和病理学
基本信息
- 批准号:10649598
- 负责人:
- 金额:$ 40.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-11 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdverse effectsAffectAnemiaAreaBinding ProteinsBiologicalCell DeathCell physiologyChildCountryDataDeveloped CountriesDevelopmentDietEducational workshopEmbryoEndocrineEndotheliumEnsureErythrocytesFerritinFetal DevelopmentFetal Growth RetardationFetusFoundationsFunctional disorderGestational DiabetesHealthHomeostasisHormonalHormonesHumanInfectionInflammationInvestigationIronIron Metabolism DisordersIron OverloadIron Regulatory Protein 1Iron deficiency anemiaLinkLong-Term EffectsMaintenanceMalnutritionMaternal HealthMaternal and Child HealthMediatingMetabolismMolecularMothersMusOxidative StressPathogenesisPathologyPathway interactionsPhysiologicalPhysiologyPlacentaPoliciesPregnancyPregnancy ComplicationsPregnant WomenPremature BirthPreventionRegulationResearch PriorityRiskRoleSamplingScienceShapesSourceSupplementationTrace metalUnited States National Institutes of Healthabsorptionadverse outcomeadverse pregnancy outcomedesignepidemiology studyfetalhealthy pregnancyhepcidinimprovediron deficiencyiron supplementationmalformationmetal transporting protein 1mouse modeloxygen transportplacental transferpregnancy disorderpreservationresponsescreeningsuccesstrophoblast
项目摘要
PROJECT SUMMARY
Adequate iron availability during pregnancy is essential for fetal development and maternal health. Iron deficiency
and its most common manifestation, anemia, are highly prevalent during pregnancy and can have adverse effects on
the mother and the fetus. Recognition of detrimental effects of iron deficiency has led to the policy of universal
iron supplementation in many countries including the US. However, in developed countries, more pregnant
women are iron-replete than iron-deficient. Indiscriminate iron supplementation in this setting may be not only
unnecessary, but may even have harmful effects related to increased oxidative stress or potential adverse
interaction with inflammation. Despite its importance, little is known about the basic physiology of iron regulation
during pregnancy, or how it is altered in complicated pregnancies.
Specific Aim 1. We will define the role of maternal and fetal hepcidin in regulating iron homeostasis during
pregnancy. Our preliminary data in mouse models indicate that maternal iron-regulatory hormone hepcidin must
be suppressed during pregnancy to ensure sufficient iron availability for placental transfer, and that trophoblast
is an important source of the hepcidin-suppressive activity. We will identify the mechanism(s) by which maternal
hepcidin is suppressed in healthy pregnancy; and determine whether maternal hepcidin levels are
inappropriately increased in human inflamed pregnancies to promote maternal iron restriction.
Specific Aim 2. Our preliminary data show that during maternal iron deficiency or excess, placental iron
transporters are regulated to ensure the maintenance of placental iron homeostasis. In response to maternal
iron deficiency in both mice and humans, this mechanism sequesters iron in the placenta at the expense of
providing adequate iron to the fetus, a phenomenon we termed the “selfish placenta”. This has important
implications for understanding the pathogenesis of fetal iron deficiency. We will define the regulatory circuitries
and biological relevance of the selfish placental response in pregnancy.
Specific Aim 3. Our preliminary data in mouse models demonstrate a dramatic adverse interaction between
maternal iron excess and maternal inflammation during pregnancy, targeting placental endothelium, and
resulting in fetal malformations and embryonic lethality. We will define the underlying mechanisms by focusing
on maternal inflammation and pregnancy hormones, as well as placental and fetal inflammation, oxidative stress,
and cell death pathways.
Our proposal will answer fundamental questions about the pathophysiology of maternal and fetal iron regulation
during pregnancy. Long-term, it has the potential to change our approaches to managing iron disorders during
pregnancy.
项目总结
孕期充足的铁供应对胎儿发育和产妇健康至关重要。缺铁
其最常见的表现是贫血,在怀孕期间非常普遍,并可能对
母亲和胎儿。认识到缺铁的有害影响导致了全民健身的政策
包括美国在内的许多国家的铁质补充剂。然而,在发达国家,更多的孕妇
女性铁质充足,而不是缺铁。在这种情况下不分青红皂白地补充铁可能不仅
不必要的,但甚至可能有与增加氧化应激有关的有害影响或潜在的不利影响
与炎症相互作用。尽管它很重要,但人们对铁调节的基本生理学知之甚少。
在怀孕期间,或者在复杂的怀孕中它是如何改变的。
具体目标1.我们将确定母体和胎儿海普西丁在调节铁稳态中的作用
怀孕了。我们在小鼠模型中的初步数据表明,母体铁调节激素海普西丁必须
在怀孕期间被抑制,以确保胎盘转移有足够的铁供应,滋养细胞
是海普西丁抑制活性的重要来源。我们将确定(S)母体通过什么机制
在健康妊娠中,海普西丁被抑制;并确定母亲的海普西丁水平是否
在人类发炎的妊娠中不适当地增加以促进母亲的铁限制。
具体目标2.我们的初步数据显示,在母亲铁缺乏或过剩期间,胎盘铁
转运蛋白被调节以确保胎盘铁稳态的维持。为了回应母体
在小鼠和人类缺铁的情况下,这种机制将铁隔离在胎盘中,代价是
为胎儿提供足够的铁,我们称之为“自私的胎盘”。这一点很重要
对了解胎儿铁缺乏发病机制的启示。我们将定义调节电路
以及孕期自私胎盘反应的生物学相关性。
具体目标3.我们在小鼠模型中的初步数据显示,
母体铁过量和妊娠期母体炎症,以胎盘内皮为靶点,以及
导致胎儿畸形和胚胎死亡。我们将通过集中精力定义潜在的机制
关于母体炎症和妊娠激素,以及胎盘和胎儿炎症,氧化应激,
以及细胞死亡途径。
我们的建议将回答有关母体和胎儿铁调节的病理生理学的基本问题。
在怀孕期间。从长远来看,它有可能改变我们在
怀孕了。
项目成果
期刊论文数量(28)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Iron overload causes a mild and transient increase in acute lung injury.
铁超负荷会导致急性肺损伤轻微且短暂的增加。
- DOI:10.14814/phy2.14470
- 发表时间:2020
- 期刊:
- 影响因子:2.5
- 作者:Zhang,Vida;Ganz,Tomas;Nemeth,Elizabeta;Kim,Airie
- 通讯作者:Kim,Airie
Enteral ferric citrate absorption is dependent on the iron transport protein ferroportin.
- DOI:10.1016/j.kint.2021.10.036
- 发表时间:2022-04
- 期刊:
- 影响因子:19.6
- 作者:Hanudel MR;Czaya B;Wong S;Rappaport M;Namjoshi S;Chua K;Jung G;Gabayan V;Qiao B;Nemeth E;Ganz T
- 通讯作者:Ganz T
Integrated regulation of stress responses, autophagy and survival by altered intracellular iron stores.
- DOI:10.1016/j.redox.2022.102407
- 发表时间:2022-09
- 期刊:
- 影响因子:11.4
- 作者:Wang, Yunyang;Wang, Mo;Liu, Yunshan;Tao, Hui;Banerjee, Somesh;Srinivasan, Shanthi;Nemeth, Elizabeta;Czaja, Mark J.;He, Peijian
- 通讯作者:He, Peijian
Iron loading induces cholesterol synthesis and sensitizes endothelial cells to TNFα-mediated apoptosis.
- DOI:10.1016/j.jbc.2021.101156
- 发表时间:2021-10
- 期刊:
- 影响因子:0
- 作者:Fisher AL;Srole DN;Palaskas NJ;Meriwether D;Reddy ST;Ganz T;Nemeth E
- 通讯作者:Nemeth E
Multiple Indicators of Undernutrition, Infection, and Inflammation in Lactating Women Are Associated with Maternal Iron Status and Infant Anthropometry in Panama: The MINDI Cohort.
- DOI:10.3390/nu14173497
- 发表时间:2022-08-25
- 期刊:
- 影响因子:5.9
- 作者:Gonzalez-Fernandez, Doris;Nemeth, Elizabeta;Pons, Emerita Del Carmen;Sinisterra, Odalis Teresa;Rueda, Delfina;Starr, Lisa;Sangkhae, Veena;Murillo, Enrique;Scott, Marilyn E.;Koski, Kristine G.
- 通讯作者:Koski, Kristine G.
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Elizabeta Nemeth其他文献
Elizabeta Nemeth的其他文献
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{{ truncateString('Elizabeta Nemeth', 18)}}的其他基金
Adverse Interaction Between Iron Deficiency and Inflammation in Pregnancy
妊娠期缺铁与炎症之间的不良相互作用
- 批准号:
10303471 - 财政年份:2021
- 资助金额:
$ 40.69万 - 项目类别:
Adverse Interaction Between Iron Deficiency and Inflammation in Pregnancy
妊娠期缺铁与炎症之间的不良相互作用
- 批准号:
10473544 - 财政年份:2021
- 资助金额:
$ 40.69万 - 项目类别:
Erythroferrone and Its Impact on Maternal and Neonatal Iron Homeostasis
赤铁酮及其对孕产妇和新生儿铁稳态的影响
- 批准号:
9760279 - 财政年份:2019
- 资助金额:
$ 40.69万 - 项目类别:
The role of iron in atherosclerosis: application of new iron biology
铁在动脉粥样硬化中的作用:新铁生物学的应用
- 批准号:
8028193 - 财政年份:2011
- 资助金额:
$ 40.69万 - 项目类别:
The role of iron in atherosclerosis: application of new iron biology
铁在动脉粥样硬化中的作用:新铁生物学的应用
- 批准号:
8208174 - 财政年份:2011
- 资助金额:
$ 40.69万 - 项目类别:
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