Developmental consequences of trace mineral deficiencies in rodents: Acute and long-term effects
Developmental consequences of trace mineral deficiencies in rodents: Acute and long-term effects
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DOI：
10.1093/jn/133.5.1477s
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发表时间：
2003-05-01
影响因子：
4.2
通讯作者：
Clegg, MS
中科院分区：
文献类型：
--
作者：
Keen, CL;Hanna, LA;Clegg, MS
大约3%的婴儿至少有一种严重的先天性畸形。在美国，平均每1000名婴儿中有10名在1岁前死亡；这些死亡中约有一半可归因于出生缺陷、出生体重过低或早产。虽然发育异常的原因显然是多因素的，但我们认为导致发育异常发生的一个共同因素是胚胎和胎儿发育期间矿物质营养不足。以锌和铜为例，有证据表明营养缺乏会迅速影响发育中的概念并导致总体结构异常。锌或铜的缺乏可导致细胞氧化还原平衡的快速变化、组织氧化应激、不适当的细胞死亡模式、神经嵴细胞迁移的改变和关键模式基因表达的变化。除了公认的畸形外，围产期发育期间的矿物质缺乏可导致行为、免疫和生化异常，并持续到成年。虽然这些持续的缺陷可以部分归因于细微的形态异常，但在其他情况下，它们可能继发于DNA甲基化模式的表观遗传或发育变化。表观遗传缺陷加上细微的形态异常会影响个人患某些慢性疾病的风险，从而影响他或她在以后的生活中发病和死亡的风险。
Approximately 3% of infants born have at least one serious congenital malformation. In the U.S., an average of 10 infants per thousand die before 1 y of life; about half of these deaths can be attributed to birth defects, low birth weight or prematurity. Although the causes of developmental abnormalities are clearly multifactorial in nature, we suggest that a common factor contributing to the occurrence of developmental abnormalities is suboptimal mineral nutrition during embryonic and fetal development. Using zinc and copper as examples, evidence is presented that nutritional deficiencies can rapidly affect the developing conceptus and result in gross structural abnormalities. Deficits of zinc or copper can result in rapid changes in cellular redox balance, tissue oxidative stress, inappropriate patterns of cell death, alterations in the migration of neural crest cells and changes in the expression of key patterning genes. In addition to well-recognized malformations, mineral deficiencies during perinatal development can result in behavioral, immunological and biochemical abnormalities that persist into adulthood. Although these persistent defects can in part be attributed to subtle morphological abnormalities, in other cases they may be secondary to epigenetic or developmental changes in DNA methylation patterns. Epigenetic defects combined with subtle morphological abnormalities can influence an individual's risk for certain chronic diseases and thus influence his or her risk for morbidity and mortality later in life.